US 2008O159999A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0159999 A1 Stefanidis (43) Pub. Date: Jul. 3, 2008

(54) COMPOSITIONS AND METHODS FOR Publication Classification IDENTIFYING, ISOLATING AND (51) Int. Cl. ENRCHING GERMLNE-LIKE STEM CELLS A6II 35/12 (2006.01) FROM AMNOTC FLUID CI2N 5/06 (2006.01) (76) Inventor: Konstantinos Stefanidis,O O Athens A6IPI/00CI2O I/68 (2006.01) (GR) A6IP 25/00 (2006.01) A6IP 43/00 (2006.01) Correspondence Address: A6IP 700 (2006.01) THE NATH LAW GROUP GOIN 33/53 (2006.01) 112 South West Street CI2O 1/02 (2006.01) Alexandria, VA 22314 (52) U.S. Cl...... 424/93.21: 435/366; 435/378: 435/6: 435/721: 435/29: 435/405 (21) Appl. No.: 11/976,321 s s s (57) ABSTRACT (22) Filed: Oct. 23, 2007 The present invention is directed to pluripotent embryonic O O stem cells derived from amniotic fluid and the methods for Related U.S. Application Data isolating, expanding and differentiating these cells, and their (60) Provisional application No. 60/853.420, filed on Oct. therapeutic uses Such as manipulating the cells by gene trans 23, 2006. fection and other means for therapeutic applications.

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COMPOSITIONS AND METHODS FOR methods for isolating, expanding and differentiating these IDENTIFYING, ISOLATING AND cells, and their therapeutic uses such as manipulating the fetal ENRCHING GERMLNE-LIKE STEM CELLS stem cells by gene transfection and other means for therapeu FROM AMNOTC FLUID tic applications. The embryonic stem cells are pluripotent and express DAZL. These cells are also characterized as germ FIELD OF THE INVENTION line-like stem cells (GLSC) due to the fact that they express 0001. The present invention relates generally to the field of DAZL. 0009. The present invention is therefore directed to DAZL stem cells. More specifically, this invention relates to isolated expressing amniotic fluid stem cells that are pluripotent and amniotic fluid pluripotent stem cell populations, and methods characterized as germline-like; methods for isolating, for identifying, isolating and enriching for Such stem cells. expanding and differentiating these cells from amniotic fluid; BACKGROUND OF THE INVENTION and culture medium that is useful for enriching for DAZL expressing amniotic fluid embryonic stem cells. 0002 Stem cells are undifferentiated cells with the ability 0010. In aspects of the invention is an amniotic fluid cell to undergo both renewal and differentiation. Stem cells composition comprising: derived from the embryo are termed embryonic stem (ES) 0.011 pluripotent embryonic stem cells expressing cells. ES cells are pluripotent and thus posses the capability of developing into any organ or tissue type or, at least poten DAZL; and tially, into a complete embryo. 0012 amniotic fluid. 0003 Pluripotent embryonic stem cells have been tradi 0013. In further aspects of the invention are isolated pluri tionally derived from embryonic sources. One type can be potent embryonic stem cells isolated from amniotic fluid that isolated from cells of the inner cell mass (ICM) at the blastula express DAZL. stage of a pre-implantation embryo (Evans and Kaufman, 0014. In aspects of the invention, there is provided a novel Nature 292,154-156, 1981; U.S. Pat. No. 6,200,806). A sec method for the isolation, identification, culture, and charac ond type can be isolated from primordial germ cells (PGCs) in terization of pluripotent embryonic stem cells from amniotic the mesenteric or genital ridges of embryos and has been fluid, these stem cells being characterized asembryonic germ termed the embryonic germ cell (EG) (U.S. Pat. No. 5.453, cells (EG) (germline-like). 357, U.S. Pat. No. 6,245,566). 0015. According to another aspect of the invention is a 0004 Human embryonic stem (hES) cells display a dis method for isolation of pluripotent embryonic stems cells tinct group of cell surface antigens such as SSEA-3, SSEA-4, expressing DAZL from amniotic fluid, the method compris TRA-2-54 (alkaline phosphatase), TRA-1-60 and TRA-1-81, ing culturing amniotic fluid cells in a medium comprising in addition to expressing specific transcription factors such as amniotic fluid and at least one growth agent for a sufficient OCT-4, NANOG, SOX-2, FGF-4 and REX-1 (Henderson, et time for at least a portion of said amniotic fluid cells to adhere al., (2002) Stem Cells 20:329-337; Draper, et al., (2002). J. to a Substrate, and further culturing non-adherent amniotic Anat. 200:249-258; Mitsui et al., (2003) Cell 113:631-642: fluid cells, identifying the amniotic fluid cells expressing at Chambers et al., (2003) Cell 113:643-655), the disclosures of least DAZL and isolating said amniotic fluid cells expressing which are incorporated by reference herein in their entirety). at least DAZL. 0005. Despite tremendous interest in ES cell research, the 0016. According to an aspect of the invention is a method destruction of embryos in order to harvest and experiment on for enriching DAZL positive stem cells from amniotic fluid. ES cells is controversial and thus the use human embryos or 0017. According to another aspect of the invention is a human fetal tissues for ES research is prohibited or strictly method for generating a population of cells enriched for pluri regulated in various jurisdictions. Therefore, there is a need potent amniotic fluid stem cells comprising isolating DAZL for a method of obtaining stem cells from an alternative positive cells from amniotic fluid and proliferating the DAZL Source that does not raise ethical concerns. positive cells in a culture medium. 0006 Amniotic fluid cells (AFC) have been suggested to 0018. According to another aspect of the invention, the be an attractive alternative to the traditional methods for GLSC expresses at least one cell Surface antigen, said at least obtaining ES cells. United States patent application one cell Surface antigen being DAZL. 20050042595 discloses a method for isolating and growing 0019. According to another aspect of the invention, the multipotent amniotic fetal stem cells from amniotic fluid GLSC expresses C-kit and SSEA-4. cells. These cells, however, are considered to be fetal mesen 0020. According to another aspect, the GLSC express cell chymal stem cells and are considered to be only multipotent, Surface antigens that bind with antibodies having the binding thus have the differentiation potential for adipogenic, osteo specificity of monoclonal antibodies Oct-4 and TRA-1-81. genic and neurogenic cell lineages (BoSsolasco et al. Cell 0021 According to an aspect of the invention is a compo Research. 2006; 16:329-336). sition and method to provide a germline like stem cell line 0007 Accordingly, there exists a need for improving characterized by expression of one or more of the following methods for identifying, isolating and growing pluripotent ES markers: DAZL(+): alkaline phosphatase(+): SSEA-1 (-); cells found in the amniotic fluid. Therefore, it is desirable to SSEA-3 (+): SSEA-4(+): TRA-1-60(+); and TRA-1-81 (+). develop new culture media and new methods for identifying, 0022. According to another aspect of the invention is a isolating and propagating pluripotent embryonic stem cells composition and method to provide a GLSC cell line having from amniotic fluid cells. the characteristics of human embryonic germ cells. 0023. According to another aspect of the invention is a SUMMARY OF THE INVENTION composition and method to provide an embryonic germ-like 0008. The present invention is directed to pluripotent stem cell line capable of proliferation in an undifferentiated embryonic stem cells derived from amniotic fluid and the state after continuous culture for at least 5-10 generations. US 2008/O 159999 A1 Jul. 3, 2008

0024. According to another aspect of the present invention 0045 (a) obtaining an amniotic fluid sample from a human is a method to provide an amniotic fluid embryonic stem cell Subject; line expressing DAZL, wherein the stem cells differentiate 0046 (b) isolating a substantially enriched population the into cells derived from mesoderm, endoderm, and ectoderm DAZL positive germline-like stem cell from the sample; and germ layers when the stem cells are injected into an immu 0047 (c) cryopreserving the isolated substantially nocompromised mouse. enriched population of DAZL positive pluripotent fetal stem 0025. According to another aspect of the present inven cells. tion, is a cell culture media that provides for long term cell 0048. According to another aspect of the present invention culture of GLSCs expressing DAZL. is a method of treating a disease in a human comprising 0026. According to another aspect of the present inven administering a Substantially enriched population of pluripo tion, the GLSCs of the present invention may be used for gene tent DAZL positive germline-like stem cells into an indi therapy and tissue engineering. vidual in need thereof. 0027. According to another aspect of the present invention 0049 According to another aspect of the present invention is the use of a Substantially enriched population of pluripotent is a use of a Substantially enriched population of pluripotent DAZL positive germline-like stem cells harvested from amni DAZL positive germline-like stem cells harvested from amni otic fluid to treat a disease in a human. otic fluid to treat a disease in a human. 0028. According to another aspect of the present invention 0050. According to another aspect of the present invention is the use of a Substantially enriched population of pluripotent is a use of a Substantially enriched population of pluripotent DAZL positive germline-like stem cells harvested from amni DAZL positive germline-like stem cells harvested from amni otic fluid in the preparation of a medicament to treat a disease otic fluid in the preparation of a medicament to treat a disease in a human. in a human. 0029. A pluripotent amniotic fluid cell composition com 0051. According to another aspect of the present invention prising amniotic fluid cells and a culture medium comprising is a composition comprising culture medium for the growth of amniotic fluid and at least one growth agent. germline-like stem cells from amniotic fluid, said culture 0030. According to another aspect of the present invention medium comprising about 20% aminotic fluid and about 80% is a method for culturing germline-like stem cells from amni basal medium, said basal medium comprising: about 80% otic fluid, said method comprising: Dulbeco's modified Eagle's medium; about 20% serum 0031 (a) culturing amniotic fluid cells on a substrate for a replacement; and wherein said culture medium is Supple sufficient time to permit a portion of said amniotic fluid cells mented with 1 mM L-glutamine, 1% nonessential amino to adhere to said substrate; acids, antibiotics and a growth agent. 0032 (b) isolating a non-adherent portion of said amniotic 0052. Other features and advantages of the present inven fluid cells; tion will be come apparent from the following detailed 0033 (b) identifying from said non-adherent portion of description. It should be understood, however, that the amniotic fluid cells cells expressing at least one germline-like detailed description and the specific examples while indicat stem marker, said at least one germline-like stem marker ing embodiments of the invention are given by way of illus being DAZL. tration only, since changes and various modifications within 0034. According to another aspect of the present invention the spirit and scope of the invention will become apparent to is a method of proliferating a population of cells enriched for those skilled in the art. pluripotent germline-like stem cells comprising: 0035 (a) growing in a first vessel, said population of cells BRIEF DESCRIPTION OF THE DRAWINGS in a culture medium; 0053. The present invention will become more fully 0036 (b) selecting and separating at least one DAZL posi understood from the detailed description given herein and tive cell from said population of cells; from the accompanying drawings, which are given by way of 0037 (c) introducing the separated said at least one DAZL illustration only and are not intended to limit the scope of the positive cell to a second vessel in said culture medium; and invention wherein: 0038 (d) proliferating said at least one DAZL positive cell 0054 FIGS. 1A-I show photomicrographs of human in said second vessel. amniotic fluid cells (AFC) culturing in Stefanidis medium. 0039. According to another aspect of the present invention After 2 days of culture (A); after 3 days of culture (B); after 4 is a method of differentiating DAZL positive germline-like days of culture (C); after 6 days of culture (D); after 8 days of stem cell comprising providing an amniotic fluid sample and culture (E); after 9 days of culture (F); after 12 days of culture inducing differentiation of DAZL positive cells within said (G); after 13 days of culture with the attached cells under sample by exposing said sample to one or more differentia investigation (H); after 13 days of culture with the floating tion-inducing agents. cells under investigation (I). 0040. According to another aspect of the present invention 0055 FIGS. 2A-C show photomicrographs of human is a method of differentiating DAZL positive pluripotent fetal embryonic germ cell colonies. After 15 days of culture (A): stem cells comprising: after 20 days of culture (B); after 28 days of culture (C). 0041 (a) providing an amniotic fluid sample: 0056 FIG.3 shows photomicrographs of human amniotic 0042 (b) obtaining cells from said sample; and fluid cells (AFC) cultured in Stefanidis medium that were 0043 (c) inducing differentiation of DAZL positive cells differentiated into human fibroblasts. from step (b) within said sample by exposing said cells to one 0057 FIGS. 4A-B show electron photomicrographs of or more differentiation-inducing agents. human germ-like stem cell (A) and a human embryoid body 0044 According to another aspect of the present invention formed from a germline-like stem cell (B). is a method for storing pluripotent fetal stem cells comprising 0058 FIG. 5 shows the flow cytometric detection of the steps of: 7AAD, DAZL and c-kit. Amniotic fluid cells were identified US 2008/O 159999 A1 Jul. 3, 2008

by two scatter regions, R1 and R2, on a forward scatter (FSC) 0068 Amniocentesis” means puncture of the amnion, the vs. side scatter (SSC) dot plot (A) and were analysed sepa thin-walled sac of fluid in which a developing fetus is sus rately for marker expression, here 7AAD" cells and the nega pended during pregnancy. tive unstained control is shown in overlay histograms (C and 0069. Anlagen' is the rudiment or the primordia of an D). Because of high degree of autofluorescence in R2 gated organ, tissue or part thereof. population (D), only R1 gated cells were used for further 0070 Antibody” as used in this invention includes intact analysis. Cells negative for 7AAD (R3) were then selected for molecules as well as fragments thereof, such as Fab, Fab', the assessment of DAZL and c-kit positive cells (B); their F(ab')2, and Fv that can bind the epitopic determinant as expression frequencies were assessed as percentages of the disclosed by Ladner et al., in U.S. Pat. No. 4,946,788. If viable amniotic fluid cells by subtracting their appropriate required, polyclonal or monoclonal antibodies can be further isotype controls (E and F). purified, for example, by binding to and elution from a matrix 0059 FIG. 6 shows photomicrographs of human embry to which the polypeptide or a peptide to which the antibodies onic germ cell (EG) colonies showing positive immunohis were raised is bound. Those of skill in the art will know of tochemical staining for: Human embryonic germ cell colo various techniques common in the immunology arts for puri nies (A1); A1 colony showing immunoreactivity to Oct-3/4 fication and/or concentration of polyclonal antibodies, as (A2); A1 colony shows immunoreactivity for stage specific well as monoclonal antibodies (See, e.g., Coligan, et al., embryonic antigen-4 (SSEA-4) (A3); Human embryonic Current Protocols in Immunology, Wiley Interscience, cur germ cell colonies (B1); B1 colonies shows immunoreactiv rent edition). “Purified antibody’ means an antibody that is at ity to a cell surface antigen that binds with the antibody least 60%, by weight, free from proteins and naturally-occur having the binding specificity of the monoclonal antibody ring organic molecules with which it is naturally associated. designated TRA-1-81 (B2); Human embryonic germ cell In aspects of the invention, the preparation is at least 75%, colonies (C1); C1 colonies show immunoreactivity to cell more preferably 90%, and most preferably at least 99%, by surface antigen DAZL (C2). weight, antibody, e.g., an anti-SSEA-1 specific antibody. The 0060 FIGS. 7A-B shows the expression of DAZL (A) and purified antibody may be obtained, for example, by affinity Oct-4 (B) mRNA expression by RT-PCR. chromatography using recombinantly-produced protein or 0061 FIG. 8 shows that GLSCs may be differentiated to conserved motif peptides and standard techniques. neurogenic cells and express the S-100 neurogenic cell 0071. “Blastocyst' is a preimplantation embryo that marker. develops froms a morula. The blastocyst has an out layer 0062 FIG. 9 shows a Cy5/Cy3 false colour image of the called the trophoblast that is required for implantation into the microarray analysis of microarray it 4800038 comparing uterine epithelium and an inner cell mass that contains the amniotic fluid-derived cells cultured according to the present embryonic stem cells and will give rise to the embryo proper. invention and human embryonic germ cells. The blastocyst contains a blastocoel or a blastocoelic cavity. 0063 FIG. 10 shows the microarray data visualized in a 0072 “Cell as used herein also refers to individual cells, doublelog scatter plot. cell lines, or cultures derived from such cells. The term "cell line' as used herein refers to human AFC or cells derived DETAILED DESCRIPTION OF THE therefrom and maintained in in vitro culture. EMBODIMENTS 0073 "Cell plating can also extend to the term “cell pas 0064. The present invention is based on using amniotic saging. Cells of the invention can be passaged using cell fluid as a source to obtain a population of stem cells which culture techniques well known to those skilled in the art. The have a pluripotent differentiation capacity and therefore area term 'cell passaging can refer to a technique that involves viable source of stem cells that can be used therapeutically. the steps of (1) releasing cells from a solid Support or Sub These cells express DAZL. The present invention discloses strate and disassociation of these cells, and (2) diluting the compositions of these cells for therapeutic use; methods of cells in media suitable for further cell proliferation. Cell isolating, enriching isolating and maintaining the cells in passaging may also refer to removing a portion of liquid culture; and therapeutic uses of the cells. An advantage of the medium containing cultured cells and adding liquid medium invention is that the cells can be efficiently isolated and propa to the original culture vessel to dilute the cells and allow gated from a source that is less controversial Such that the further cell proliferation. In addition, cells may also be added method overcomes the ethical considerations associated with to a new culture vessel which has been supplemented with traditional known methods used to harvest embryonic stem medium suitable for further cell proliferation. cells. The ability of maintaining the cells of the invention as 0074 “Conditioned medium” refers to a growth medium cell lines permits clinical investigation of these cells and the that is further supplemented by factors derived from media dynamics of interaction in their cellular and chemical envi obtained from cultures offeeder cells on which human AFC rOnment. can be cultured. 0065 Various terms are used herein in this application 0075 "DAZL (deletion in azoospermia like) is a marker which are generally defined as follows and are well known by expressed in embryonic germ cells. The gene encodes RNA one of skill in the art: binding proteins. DAZL gene expression is unique as it is 0066 “Amniotic fluid or amniotic fluid samples' means expressed before meiosis in male and female gonads. This samples of fluid obtained from within the amnion. The amni pattern of expression suggests that these genes participate in otic fluid may or may not be filtered from cellular material, the early proliferation, differentiation and maintenance of Such as cells. male and female embryonic germ cells. 0067 “Amniotic Fluid-Derived Cells or Amniotic Fluid (0076 “Embryonic germ cells” or “EG cells' are cells Cells (AFC) are cells that are contained in amniotic fluid derived from primordial germ cells (PGCs). The term samples obtained during amniocentesis at, for example, about "embryonic germ cell is used to describe cells of the present 17-22 weeks of gestation. invention that exhibit an embryonic pluripotent cell pheno US 2008/O 159999 A1 Jul. 3, 2008

type. The terms “human embryonic germ cell (EG) or 0087) “Proliferation as used herein in reference to cells "embryonic germ cell can be used interchangeably herein to can refer to a group of cells that can increase in number over describe human cells, or cell lines thereof, of the present a period of time. invention that exhibit a pluripotent embryonic stem cell phe I0088 “Recombinant product as used herein can refer to notype as defined herein. Thus, EG cells are cells capable of the product produced from a DNA sequence that comprises at differentiation into cells of ectodermal, endodermal, and least a portion of the modified nuclear DNA. This product can mesodermal germ layers. EG cells can also be characterized be a peptide, a polypeptide, a protein, an enzyme, an antibody, by the presence or absence of markers associated with spe an antibody fragment, a polypeptide that binds to a regulatory cific epitope sites identified by the binding of particular anti element (a term described hereafter), a structural protein, an bodies and the absence of certain markers as identified by the RNA molecule, and/or a ribozyme, for example. lack of binding of certain antibodies. 0089 “Stefanidis medium’ means a novel stem cell cul 0077. "Embryoid body” (EB) is a three dimensional struc ture medium capable of Supporting growth of human AFCs ture that forms from differentiated embryonic stem cells. and GLSCs expressing DAZL as well as other markers. Cellular derivatives of all three germ layers have been gener According to an aspect of the invention, Stefanidis medium is ated from embryoid bodies, such as hematopoietic, endothe prepared using about 20% amniotic fluid with 80% basal lial, muscle and neuronal cells. medium, itself comprising 80% Dulbeco's modified Eagle's 0078. “Epitope' means any antigenic determinant on an medium (DMEM) (Gibco BRL, Rockville, Md.) supple antigen to which the paratope of an antibody binds. Epitopic mented with 20%. KnockCut SR, a serum-free replacement determinants usually consist of chemically active Surface originally optimized for human ES cells (Gibco BRL, Rock groupings of molecules Such as amino acids or Sugar side ville, Md.), 1 mM L-Glutamine, 1% nonessential amino chains and usually have specific three dimensional structural acids stock (Gibco BRL, Rockville, Md.), penicillin and characteristics, as well as specific charge characteristics. streptomycin and 4 ng/mlbFGF. 0079. “Feeder cells' as used herein can refer to cells that are maintained in culture and are co-cultured with target cells. DAZL-Expressing Pluripotent Stem Cells, Compositions Target cells can be embryonic germline-like stem cells and Thereof and Stem Cell Culture Medium cultured cells for example. Feeder cells (e.g. fibroblasts) can 0090 The invention provides pluripotent embryonic stem provide, for example, peptides, polypeptides, electrical sig cells isolated from amniotic fluid wherein the cells express nals, organic molecules (e.g., steroids), nucleic acid mol one or more markers for pluripotent embryonic germ cells ecules, growth factors (e.g., bFGF), other factors (e.g., cytok including DAZL. In another aspect of the invention, the cells ines such as LIF and steel factor), and metabolic nutrients to also express SSEA-4, TRA-1-60 and Oct-4 markers as dem target cells. Feeder cells, in aspects of the invention, grow in onstrated by a variety of methods known to those of skill in a mono-layer. the art such as but not limited to reverse-transcription (RT 0080 “Germline-like stem cell or embryonic germline PCR), immunofluorescence (IF), or methods of analysis of like stem cell (GLSC) are pluripotent or multipotent stem differential gene expression, microarray analysis and related cells. These cells possess characteristics of pluripotent techniques. According to aspects of the invention, the cells embryonic stem (ES) cells and embryonic germ cells (EG). maintain a normal karyotype during prolonged cultivation in 0081 “Long term' refers to a cell culture of more than 30 vitro. days. 0091. The pluripotent embryonic stem cells of the inven I0082 “Multipotent” refers to cells that are capable, tion in addition to at least expressing DAZL (and other mark through its progeny, of giving rise to several different cell ers) may also express the c-kit receptor. The c-kit receptor types. protein, also known as c-Kit receptor, Steel factor receptor, 0.083 "Non-essential Amino acids’ refers to the amino stem cell factor receptor and CD 117 in standardized termi acids L-alanine, L-asparagine, L-aspartic acid, L-glutamic nology of leukocyte antigens, is constitutively expressed in acid, L-glycine, L-proline, and L-serine. hematopoietic stem cells and germ cells. The c-kit receptor I0084) “Primordial germ cells” (PGCs) is used to describe plays a fundamental role during the establishment, mainte undifferentiated embryonic germ cells isolated over a period nance and function of germ cells. In the embryonal gonad, the of time post-fertilization from anlagen or from yolk sac, c-kit receptor and its ligand SCF are required for the survival mesenteries, or gonadal ridges of human embryoS/fetus. and proliferation of primordial germ cells. PGCs are the source from which EG cells are derived. Gono 0092. In accordance with the present invention, the cytes of later testicular stages also can be useful sources of embryonic stem cells are obtained from human amniotic PGCS. fluid. Large quantities of amniotic fluid cells can be obtained I0085 “Pluripotent” refers to cells that retain the develop from Subjects during pregnancy and/or at birth depending on mental potential to differentiate into a wide range of cell which cell source is used. The stem cells obtained from these lineages including the germline. The terms "embryonic stem sources may be cultured in various media, such as DMEM, cell phenotype' and "embryonic stem-like cell also are used F-12, M199, RPMI and combinations thereof, supplemented interchangeably herein to describe cells that are undifferen with fetal bovine serum (FBS), whole human serum (WHS), tiated and thus are pluripotent cells and that are capable of or Supplemented with growth factors, cytokines, hormones, being visually distinguished from other adult cells of the Vitamins, antibiotics, or any combination thereof. A novel same animal. Stefanidis medium as herein described is preferred either I0086) “Plated” or “plating” as used herein in reference to alone or in combination with any of the elements recited cells can refer to establishing cell cultures in vitro. For Supra. example, cells can be diluted in cell culture media and then 0093. The embryonic stem cells of the invention may also added to a cell culture plate, dish, or flask. Cells may be plated be expanded in the presence of an agent which suppresses at a variety of concentrations and/or cell densities. cellular differentiation. Such agents are well-known in the art US 2008/O 159999 A1 Jul. 3, 2008

(Dushnik-Levinson, M. et al., “Embryogenesis in vitro: replacement medium. The source of the amniotic fluid may be Study of Differentiation of Embryonic Stem Cells.” Biol. from any type of animal such as, but not limited to mammals. Neonate, Vol. 67, 77-83, 1995, the disclosure of which is In another aspect of the invention, the Source may be from a incorporated herein by reference). Examples of agents which primate. In one aspect, the source of the amniotic fluid is suppress cellular differentiation include leukemia inhibitory human. The amniotic fluid may be obtained at any time of the factor (LIF) and stem cell factor. On the other hand, agents gestational period or at birth as desired. In aspects, there is such as hydrocortisone, Ca", keratinocyte growth factor provided about 5% to about 50% amniotic fluid in the (KGF), TGF-B, retinoic acid, insulin, prolactin, sodium medium. butyrate, TPA, DIVISO, NMF, DMF, collagen, laminin, 0098. The basal growth medium can be selected from any heparan SO, androgen, estrogen, and combinations thereof suitable commercially available medium such as but not lim may be used to induce differentiation (Culture of Epithelial ited to Dulbecco's Modified Eagle Medium (“DMEM), Cells, (R. Ian Freshney ed., Wiley-Liss 1992)). Basal Media Eagle (BME), DMEM/F-12 (1:1 DMEM and 0094 Furthermore, the cells of the invention may also be F-12 vol:Vol); Medium 199: F-12 (Ham) Nutrient Mixture: cultured in the presence of one or more of the following at the F-10 (Ham) Nutrient Mixture; Minimal Essential Media stated final concentration: forskolin (3R-(3C.4C.f3, 5B, 6B, (MEM), Williams' Media E; and RPMI 1640, all of which are 6ao, 10C., 10C.f3, 10bo)-5-(acetyloxy)-3-ethenyldodecahy available from Gibco BRL/Life Technologies, Inc. (Gaith dro-6,10,10b-trihydroxy-34a, 7.7.10a-pentamethyl-1H ersburg, Md.). naphtho2,1-bipyran-1-one) at 10 uM, cholera toxin at 10 0099. In the methods of the present invention, the isolation uM, isobutylmethylxanthine (IBMX) at 0.1 mM, dibutyrlad and propagation of pluripotent embryonic stem cells express enosine cyclic monophosphate (dbcAMP) at 1 mM. Other ing DAZL may be done without adding serum to the culture suitable agents for use in the invention are described in Inter medium. Therefore, according to a further aspect of the inven national Patent Application, WO 2005/017117, and herein tion, the basal growth medium may comprise about 50% to incorporated by reference in its entirety. about 90% serum replacement medium. In aspects of the 0095. The cells may be assessed for viability, proliferation invention, Knockout SerumTM replacement (Gibco) is used. potential, and longevity using standard techniques in the art. 0100. In aspects the Stefanidis medium comprises about For example, a trypanblue exclusion assay, a fluorescein diac 80% DMEM and about 20% serum replacement medium of etate uptake assay, a propidium iodide uptake assay, or other the basal growth medium. The use of other basal growth techniques known in the art may be used to assess viability. A media suitable that would be suitable for growth of the amni thymidine uptake assay, an MTT cell proliferation assay, or otic fluid cells of the present invention will be readily appar other techniques known in the art may be used to assess ent to those skilled in the art. A variety of agents such as, but proliferation. Longevity may be determined by the maximum not limited to IGF-1, IGFBP-2, inhibin B, T4, taurine, corti number of population doublings in extended cultures or other sol, MCP-1 may also be included in the Stefanidis medium. techniques known in the art. Additionally, cells of different The Stefanidis medium may also contain at least one of lineages may be derived by inducing differentiation of fetal non-essential and essential amino acids; a pyruvate salt; a stem cells and as evidenced by changes in cellular antigens. reducing agent and combinations thereof. In aspects the Various differentiation-inducing agents are used to accom amino acid is L-glutamine. plish Such differentiation, such as growth factors (for example 0101. It will be apparent to those in the art that certain EGF, AFGF, bFGF, PIDGF, TGFB), hormones (including but changes in the specific chemical components employed in the not limited to insulin, triiodothyronine, hydrocortisone, and preparation of Stefanidis medium can be tolerated without dexamethasone), cytokines (for example IL-1C. or P. IFN-y, affecting the function or altering the effectiveness of the TFN), matrix elements (for example collagen, laminin, hepa medium. Also, it will be appreciated that numerous non ran sulfate, Matrigel), retinoic acid, transferrin, TPA, and nutrient materials, e.g., antibiotics, can be added to a growth DMSO. Such differentiation-inducing agents are known to medium without affecting the basic functionality of the those of ordinary skill in the art (Culture of Epithelial Cells, medium. It will also be understood that certain components of (R. Ian Freshney ed., Wiley-Liss 1992)). Identification of the medium or the serum-free supplements can be substituted differentiated cells may be accomplished by staining the cells by equivalent substances or by preparations from different with tissue-specific antibodies according to techniques sources or with minor deviations of purity without affecting known in the art. the functionality of the medium. Any Such substitutions and 0096. The present invention is also directed to composi additions are contemplated to be encompassed herein. Also, it tions comprising the embryonic stem cells expressing DAZL. will be understood that the medium of the instant invention In aspects, the composition comprises embryonic stem cells can be prepared in a number of different ways known to those expressing DAZL, amniotic fluid cells and a novel stem cell of ordinary skill in the art. For example, it can be prepared as culture medium. The stem cell culture medium (hereinafter one or more concentrated Stock mixtures or Solutions and then combined and diluted out as desired. Further, it is con referred to as StefanidisTM medium) of the present invention templated that the medium can be subjected to different comprises amniotic fluid and one or more growth factors, physical treatments, for example, autoclaving, filtration, lyo cytokines, hormones, vitamins, antibiotics, cellular agents, philization, etc., and may be used as Such with complete chemicals or any combination thereof. equivalence. 0097. The present invention is also directed to a novel cell culture medium that is particularly advantageous for the iso lation and propagation of the cells of the invention. The Amniotic Fluid Cells and Germline-Like Stem Cells and medium, Stefanidis medium, comprises amniotic fluid; at Methods of Cell Culture least one or more growth factors, cytokines, hormones, Vita 0102. In one embodiment, the invention provides for a mins, antibiotics, cellular agents, chemicals or any combina method of growing amniotic fluid cells (AFC) and isolating tion thereof basal growth medium; and optionally a serum embryonic stem cells expressing DAZL from the amniotic US 2008/O 159999 A1 Jul. 3, 2008 fluid. As disclosed, the pluripotent embryonic stem cells of can be pluripotent stem cells characterized by a) the ability to the invention feature many of the characteristics of pluripo grow in continuous culture, and b) the presence of at least one, tent embryonic germ cells. The present invention provides an or two, or three, or four, or five, or all of the markers selected alternative source of human ES cells, thus eliminating the from the group consisting of SSEA3, SSEA4, Tra1-60, Tra1 requirement to produce or disaggregate a normal, competent 81, Tra2-54, and Oct-4. The stem cells can further express at embryo. least one marker selected from the group consisting of HLA 0103 Samples of amniotic fluid (5-15 ml) were obtained Class I, CD13, CD44, CD49b, and CD105 as disclosed in after ultrasonography-guided amniocentesis performed on U.S. Pat. No. 5,677,136, herein incorporated by reference in pregnant women with a gestational age ranging from 17 to 22 its entirety. weeks. The samples were centrifuged at 1800 rpm for 5 0111 Importantly it was also shown that at least one germ minutes twice, and the pellets removed and resuspended in 10 cell specific gene DAZL, was expressed by human ES cells ml of Stefanidis medium as described in the examples sec but not by human ICM. The existing gene expression data are tion, in a 75 cm flask and incubated at 37° C. with 5% consistent with the idea that the closest in vivo equivalent to humidified CO. After about 96 hours to about 128 hours, the ES cells clearly is not the ICM or primitive ectoderm but an non-adhering portion of amniotic fluid cells in the Superna early germ cell. The present results are in agreement with a tant was collected. The non-adherent portion of amniotic cells review article from James Thomson titled “a germ cell origin were centrifuged and plated in a) 5 ml of Stefanidis medium of embryonic stem cells” (Development 2005; 132:227-233). (flask-A) or b) 5 ml of DMEM-high glucose supplemented Human ES cells in a population express the early germ cell with 20% fetal bovine serum and glutamine and basic fibro markers related (STELLA) and deleted in azoospermia like blast growth factor (4 ng/ml) (flask-B) in 25 cm flask and (DAZL), indicating that a minor subset of randomly differ incubated at 37°C. with 5% humidified CO. entiating cells in a minor Subset of randomly differentiating 0104. As can be seen in FIGS. 1A-I, the colonies of GLSC cells in a mixed population is mot responsible for the expres began to appear 10-20 days after plating the non-adhering sion of germ cell markers in ES cell cultures. amniotic fluid cells in the culture flask-A containing Stefani 0112 The DAZL gene, known also as DAZL.1, DAZLA or dis medium. Human fibroblasts began to appear in the culture DAZH, is an autosomal homolog of the DAZ (Deletion in flask-B. AZoospermia) gene present on the Y chromosome (Saxena, 0105 Morphologically, the GLSCs formed 4-6 well R. et al. Nature Genet. 14, 292-299, 1996). These genes defined colonies and resembled ES cells, with a small cyto encode RNA binding proteins, found to be expressed specifi plasm-to-nuclear ration and multiple nucleoli and cytoplas cally in germ cells in the testis. Later studies have demon mic lipid bodies (FIGS. 2A-C). strated that the DAZL gene expression is unique as it is 0106 Alpha-fetoprotein and the beta-subunit of human expressed before meiosis in male and female gonads (Selig chorionic gonadotrophin were readily detected by immu man and Page, Biochem. Biophys. Res. Corn. 245, 878-82, noassay in the Supernatants of the GLSC cultures grown to 1998). This pattern of expression suggests that these genes high density. Alpha-fetoprotein is a characteristic product of participate in the early proliferation, differentiation and main endoderm cells and human chorionic gonadotrophin secre tenance of male and female germ cells. Expression studies of tion is characteristic of trophoblastic differentiation. a DAZL homolog in the mouse, denoted Dazl, Suggest that 0107. By flow cytometry analysis it was found that about this gene is expressed as early as when primordial germ cells of 15-30% of fresh amniotic fluid cells express DAZL (FIG. appear in the developing embryonic gonads. The similarity 5). It was also found that these GLSC have medium-large between the DazI and DAZL expression in male and female volume and express Oct-4. Furthermore, in the study it was gonads Suggests that DAZL gene is expressed in early human observed with flow cytometry analysis that a subpopulation gonad development as well, presumably in primordial germ within amniotic fluid cell samples can be found to be Oct-4 cells. and SSEA-4 positive. The fact that only -0.2% of the cells 0113. Numerous genes are known to be expressed exclu expresses the two molecular markers of Oct-4 and SSEA-4 sively in male or female germ cells, mainly in meiotic or Suggests that only a distinct Subpopulation of amniotic fluid postmeiotic cells, but not in the earliest stages of gametoge cells is embryonic-like stem cells at 17-22 weeks of gestation. nesis. The expression of the human DAZL gene in both male 0108. The GLSCs have strong expression of molecular and female germ cells so early during embryonic develop markers of DAZL, and Oct-4 and SSEA-4, and TRA-1-60, ment is unusual. In the mouse, only a very few genes are and also express Oct-4 mRNA. In contrast human fibroblast known to be expressed exclusively in male and female germ cells did not express molecular markers of Oct-4 and SSEA-4 cells early during gametogenesis, but no human homologous and also did not express Oct-4 and mRNA (FIGS. 6A1-C2). genes were studied. The mouse germ cell nuclear antigen 0109 The resulting GLSCs can be maintained in an undif (GCNA1) is expressed in primordial germ cells, and later in ferentiated state for at least two months in culture and may be oogonia and prospermatogonia, as is the DAZL gene, but no cultured for at least about 5-10 generations. DNA sequences of GCNA1 are available (Endres and May, 0110. The amniotic fluid-derived cells can be pluripotent Dev. Biol. 163,331-340, 1994). The TIAR gene, which is also stem cells or multipotent stem cells. For example, the amni an RNA-binding protein such as DazI, was found to be otic fluid-derived cells can be multipotent stem cells charac expressed in primordial germ cells (Beck, A. R. P. et al. Proc. terized by a) the ability to grow in continuous culture and b) Natl. Acad. Sci. USA95, 2331-2336, 1998). the presence of at least one, or two, or three, or four, or five, or 0114. According to another aspect of the invention, the all of the markers selected from the group consisting of cells of the present invention do not require feeder layers to SSEA-3, SSEA-4, Tra1-60, Tra1-81, Tra2-54, and Oct-4. grow and also do not require the presence of serum. Further These stem cells can further express at least one marker more, by modifying culture conditions, the cells of the inven selected from the group consisting of: HLA Class I, CD13, tion or fibroblasts could be generated in vitro, from AFCs. CD44, CD49b, and CD105. The amniotic fluid-derived cells Throughout the process and at its end, the human ES cells US 2008/O 159999 A1 Jul. 3, 2008 retain normal karyotypes. While not wishing to be bound to or gene array may be carried out to determine expression of any particular theory, it may be hypothesized that the pluri stem cell specific genes such as Oct-4. potent embryonic stem cells of the invention expressing I0122. In a particularly advantageous embodiment of the DAZL most closely represent early germ cells. present invention, the cells of the invention can be propagated 0115 The conclusions that could be drawn from these for an indefinite period of time in continuous culture in an findings are that amniotic fluid samples contain pluripotent undifferentiated state. The term “undifferentiated’ refers to stem cells such as embryonic-like stem cells and differenti cells that have not become specialized cell types. The cells ated cells. In an aspect of the invention the Source of amniotic may be grown in an undifferentiated State for as long as fluid may be mammalian. In another aspect of the invention, desired and can then be cultured under certain conditions to the source may be from a primate. In yet another aspect, the allow progression to a differentiated state. The term “differ Source is human. entiation' is meant by the process whereby an unspecialized 0116. In another aspect, the invention provides a method cell acquires the features of a specialized cell Such as but not for Screening agents that induce the pluripotent embryonic limited to fat cells, cardiac muscle cells, epithelial cells, liver stem cells expressing DAZL to differentiate. In one aspect of cells, brain cells, blood cells, neurons, glial cells, pancreatic the method, components including the compound and at least cells, and the like. one cell of the invention are incubated under conditions suf I0123 General methods relating to stem cell differentiation ficient to allow the components to interact. The effect of the techniques that may be useful for differentiating the GLSCs compound on the cells is determined before and after incu of this invention can be found in general texts such as: Tera bating in the presence of the compound. The appearance in tocarcinomas and embryonic stem cells: A practical approach culture of a restricted developmental lineage cell indicates (E. J. Robertson, ed., IRL Press Ltd. 1987); Guide to Tech differentiation of the cells by the compound. niques in Mouse Development (P. M. Wasserman et al. eds., 0117. Another aspect of the present invention provides Academic Press 1993); Embryonic StemCell Differentiation methods for selection of pluripotent or multipotent amniotic in vitro (M.V. Wiles, Meth. Enzymol. 225:900, 1993); Prop fluid stem cells using the DAZL mRNA as a marker. Labeled erties and uses of Embryonic StemCells Prospects for Appli oligonucleotide or polynucleotide probes or antibodies, or cation to Human Biology and Gene Therapy (P. D. Rathjen et other agents which selectivity bind said mRNA may be used al., Reprod. Fertil. Dev. 10: 31, 1998); and in Stem cell for labelling DAZL positive cells and separating them using biology (L. M. Reid, Curr. Opinion Cell Biol. 2: 121, 1990), methods known in the art. each of which is incorporated by reference herein in its 0118. The DAZL specific antibodies, in aspects of the entirety. invention are monoclonal antibodies and can be used to sepa 0.124. As stated previously, differentiation-inducing rate germ stem cells by separation methods known in the art. agents, maturation agents, or maturation factors may be use 0119. In another aspect, a selectable marker such as DAZL ful to allow progression to certain cell types. Examples of is expressed in a restricted developmental lineage cell. The differentiation inducing agents, that may be used include but restricted developmental lineage cell contains a recombinant are not limited to agents, such as N-butyrate, which are useful polynucleotide that encodes the selectable marker such that for differentiating embryonic stem cells to liver cells are the marker is expressed from a restricted developmental lin described in U.S. Pat. No. 6,506,574, to Rambhatla et al. eage cell specific promoter. The DAZL positive GLSCs of the Optionally, maturation agents, or maturation factors, such as, present invention may serve as tools to identify new develop for example, growth factors, peptide hormones, cytokines, mental lineage specific cells and their associated promoters ligand receptor complexes, corticosteroids, retinoic acid, and Such as but not limited to lines of spermatogonia and oogonia. even organic solvents like DMSO have been found to effect 0120 In aspects of the invention, the pluripotent embry differentiation of embryonic stem cells (U.S. Pat. No. 6,506, onic stem cells of the invention line will constitute a purified 574). Other suitable differentiating or maturation agents preparation of an undifferentiated stem cell line. In another which may be used include but are not limited to a glucocor aspect of the invention, the stem cell line is a permanent cell ticoid with cAMP-elevating agents, methyl-isobutylxan line, distinguished by the characteristics identified above. thine, indomethacin, and the like. They have normal karyotype along with the characteristics 0.125. The pluripotent embryonic stem cells of the inven identified above. This combination of defining properties will tion expressing DAZL provide an excellent model system to identify the cell lines of the invention regardless of the understand the differentiation, development and functioning method used for their isolation. According to another aspect of gonads. For instance, the cells may be differentiated into of the invention, the GLSC lines differentiate into cells oocytes or spermatocytes using techniques well known by derived from mesoderm, endoderm, and ectoderm germ lay those in the art. Once oocytes are obtained, they may be ers when the cells are injected into an immunocompromised enucleated. Somatic cell nuclei are obtained from an infertile mouse. The methods used to inject into an immunocompro female patient to be treated and somatic cell transfer is then mised mouse are well known to those in the art. performed. Blastocysts are then obtained from which stem 0121 Methods of identifying the characteristics of the cells which are genetically identical to the infertile female are cells of the invention are well known to the skilled addressee. isolated. Such stem cells are then treated as described herein Methods such as (but not limited to) indirect immunofluores to generate a second generation of germ cells. The germ cells cence or immunocytochemical staining may be carried out on are subjected to culture conditions which promote the forma colonies of GLSCs which are fixed by conventional fixation tion of oocytes which can then be used in in vitro fertilization protocols then stained using antibodies against stem cell spe methods. cific antibodies and visualized using secondary antibodies 0.126 Gametes derived from the cells of the invention may conjugated to fluorescent dyes or enzymes which can produce be made relatively inexpensively and may be scientifically insoluble colored products. Alternatively, RNA may be iso and socially invaluable for biomedical research. Customized lated from the stem cells and RT-PCR, Northern blot analysis gametes may offer new reproductive choices to individuals US 2008/O 159999 A1 Jul. 3, 2008

who desire to have children. Gametes derived from the dif culture and grow fibroblasts from every amniocentesis ferentiation of the cells may be created and cultured in large sample. The applicants successfully split fibroblasts for many quantities using bioreactors. Thus the cells of the invention generations. The newly formed fibroblasts may be cryopre can be a valuable ethical and practical cell source for fetal served and thawed with about a 60% survival rate. These tissue engineering. differentiated fibroblasts have a normal karyotype and may be 0127. In another aspect of the present invention, the inven used as a feeder line to grow the inner cell mass from mouse tion also discloses cell culture medium and methods for grow blastocysts and finally human inner cell mass from a blasto ing and maintaining cultures of AFC, which includes the cyst. pluripotent embryonic stem cells of the invention. The Ste 0.132. According to another embodiment of the present fanidis medium also provides for the growth and maintenance invention, GLSC may be injected into SCID mice such as by of stem cells expressing DAZL and can be used to screen for subcutaneous injection into the legs. The injection of GLSC additional growth factors and useful combinations of growth of the present invention will result in the formation of terato factors. The ability to grow the cells in a substantially undif carcinomas. ferentiated State using the cell culture media, growth factors, 0.133 According to another embodiment of the invention, and methods provided herein provides important benefits the GLSC may also be cryopreserved in a cell bank for poten including the ability to produce cell lines. tial future use. The methods of cryopreserving embryonic 0128. According to an embodiment of the present inven stem cells are well known by those skilled in the art as exem tion, the pluripotent embryonic stem cells may be grown in plified by WO 2005/017117 and may be used to cryopreserve the presence of feeder cells. In aspects of the invention, the the GLSC of the present invention. feeder cells can be first grown to confluence and then mitoti 0.134 Essentially all of the uses known or envisioned in the cally inactivated (e.g., by irradiation) to prevent further prior art for stem cells, can be accomplished with the amniotic growth of the feeder cells. Such an approach has the advan fluid derived GLSC of the present invention. These uses tage of simplifying the management of the cell culture as the include diagnostic, prophylactic and therapeutic techniques. growth of only one set of cells, the EG cells, need only be monitored. Treatment 0129. Once established, the cells can be cultured under the 0.135 The isolated pluripotent embryonic stem cells above-described conditioned medium using a variety of tech expressing DAZL cells from the amniotic fluid cells or their niques. According to an embodiment of the invention, a con derivatives may in various regimes to treat diseases in humans tainer holds feeder cells in a non-conditioned medium. A or animals. As used herein the term “treat' or “treatment matrix of lysed feeder cells is prepared using standard meth refer to both therapeutic treatment and prophylactic or pre ods well known to those of skill in the art. The pluripotent Ventative measures, wherein the object is to prevent, slow embryonic stem cells expressing DAZL to be cultured are down (lessen), or reverse an undesired physiological change then added atop the matrix along with the conditioned or disorder. The term “treat also refers to the characterization medium. Alternatively, the pluripotent embryonic stem cells of the type or severity of disease which may have ramifica expressing DAZL can be grown on living feeder cells using tions for future prognosis, or need for specific treatments. For methods known in the art. The growth of the pluripotent purposes of this invention, beneficial or desired clinical embryonic stem cells expressing DAZL is then monitored to results include, but are not limited to, alleviation of symp determine the degree to which the cultured cells have become toms, diminishment of extent of disease, stabilized (i.e. not differentiated. A marker for alkaline phosphatase is used to worsening) state of disease, delay or slowing of disease pro ascertain which cells have differentiated, all of which are gression, amelioration or palliation of the disease state, and commonly known and practiced by those of skill in the art remission (whether partial or total), whether detectable or (Kaplan, O. L. etal Stem Cells. 2006 February; 24(2):266-73: undetectable. Itskovitz-Eldor 3, et al. Mol. Med. 2000 February; 6(2):88 0.136 “Treatment can also mean prolonging survival as 95). When a sufficient number of cells have differentiated, or compared to expected Survival if not receiving treatment. when the culture has grown to confluence, at least a portion of Those in need of treatment include those already with the the undifferentiated cells can be passaged. The determination condition or disorder as well as those prone to have the to passage the cells and the techniques for accomplishing condition or disorder or those in which the condition or dis Such passaging can be performed using standard techniques order is to be prevented. well known in the art. 0.137 To treat a human or animal in need of treatment, the 0130. While not being limited to any theory, it is believed cells can be either regenerated into segments of a desired that the pluripotent embryonic stem cells expressing DAZL tissue, then transplanted into the patient, or can be regener are mainly found in the non-adherent portion after about 96 to ated into a whole tissue that will be used to replace the failing about 128 hours of plating in Stefanidis medium. Interest tissue, or can be injected into a tissue of interest as whole ingly, embryonic stem cells have been obtained using the cells, where they will regenerate at the injected location. adherent cell portion when grown in the presence offibroblast 0.138. It may be possible to replace any type of failing feeder lines (at 128 hours). Further, these embryonic stem tissue with the cells of the present invention. Pluripotent cells also attach to the fibroblast feeder lines and may them embryonic stem cells expressing DAZL may be differentiated selves be further differentiated into fibroblasts. into tissues such as liver, endocrine tissues, lung, blood cells, 0131. According to another aspect of the invention, the neuronal or astroglial cells, spermatocytes, oocytes or others, methods disclosed permit the culture and the formation of which may then be used for transplantation to cure or treat fibroblasts from AFC. It has been known that fibroblastic cells diseases. cannot be cultivated from every amniocentesis sample (Hen 0.139 Examples of diseases that may be treated with the gatschläger. J Reproduktionsmed Endocrinol 2005; 4:233-8). cells of the invention and tissues include but are not limited to The applicants have disclosed compositions and methods to infertility, cirrhosis of the liver, pancreatitis, diabetes, Parkin US 2008/O 159999 A1 Jul. 3, 2008

son's disease, spinal cord injury, stroke, burns, heart disease, Current Protocols in Molecular Biology and Short Protocols certain types of cancer, osteoarthritis, rheumatoid arthritis, in Molecular Biology, 3rd Edition (F. M. Ausubel et al., eds., leukemia, lymphoma, genetic blood disorders, and brain dis 1987 & 1995); and Recombinant DNA Methodology II (R. orders such as Alzheimer's disease. Additional examples of Wu ed., Academic Press 1995); each of which is incorporated diseases that can be treated with amniotic fluid-derived by reference herein in its entirety. GLSCs include but are not limited to Acute Lymphoblastic 0142. The methods used to perform the genetic modifica Leukemia, Acute Myelogenous Leukemia, Acute Bipheno tions to the cells can be any of those known in the molecular typic Leukemia, and Acute Undifferentiated Leukemia; biological arts for making genetic alternations. Such methods Chronic Myelogenous Leukemia, Chronic Lymphocytic include, but are not limited to, the use of positive-negative Leukemia, Juvenile Chronic Myelogenous Leukemia, Juve selector vectors as described in U.S. Pat. Nos. 5,464,764; nile Myelomonocytic Leukemia, Refractory Anemia, Refrac 5.487,992: 5,627,059; and 5,631,153 to Capecchi, et al.; and tory Anemia with Ringed Sideroblasts, Refractory Anemia U.S. patent application Ser. No. 08/781,559. In addition, with Excess Blasts, Refractory Anemia with Excess Blasts in yeast artificial chromosomes (YACs) can be employed to Transformation, Chronic Myelomonocytic Leukemia, Aplas perform genetic modifications as described in U.S. patent tic Anemia, Fanconi Anemia, Paroxysmal Nocturnal Hemo application Ser. Nos. 08/597.532; 08/397.547; 08/187,161; globinuria, Pure Red Cell Aplasia, Acute Myelofibrosis, 08/276,565; 08/375,482; 08/485,505; and 08/372,482. Agnogenic Myeloid Metaplasia, myelofibrosis, Poly 0.143 Furthermore, isogenic DNA constructs can be used cythemia Vera, Essential Thrombocythemia, Non-Hodgkin’s with the GLSC cultured using the methods and materials Lymphoma, Hodgkin's Disease, Chediak-Higashi Syn provided by the present invention as described in U.S. patent drome, Chronic Granulomatous Disease, Neutrophil Actin application Ser. No. 08/563,138. Still other methods include Deficiency, Reticular Dysgenesis, Mucopolysaccharidoses, those described in U.S. Pat. No. 5,591,625 to Gerson, et al. for Hurler's Syndrome, Scheie Syndrome, Hunter's Syndrome, the preparation stem cells capable of augmented expression Sanfilippo Syndrome, Morquio Syndrome, Maroteaux-Lamy of certain gene products, signal transduction molecules, cell Syndrome, Sly Syndrome, Beta-Glucuronidase Deficiency, Surface proteins and the like for therapeutic applications. Adrenoleukodystrophy, Mucolipidosis II, Krabbe Disease, 0144. In another aspect, the present invention provides Gaucher's Disease, Niemann-Pick Disease, Wolman Disease, useful pharmaceutical products produced by the cells or cell Metachromatic Leukodystrophy, Familial Erythrophagocytic lines of the present invention, including cells and cell lines Lymphohistiocytosis, Histiocytosis-X, Hemophagocytosis, derived from GLSC comprising one or more genetic modifi Inherited Erythrocyte Abnormalities, Beta Thalassemia cations and/or their gene products. In aspects of the invention, Major, Sickle Cell Disease, Inherited Immune System Disor inhibitors of reverse transcriptase Such as nevirapine may be ders, Ataxia-Telangiectasia, Kostmann Syndrome, Leuko used to introduce a genetic modification in the cells. One cyte Adhesion Deficiency, DiGeorge Syndrome, Bare Lym skilled in the art would understand that there may be other phocyte Syndrome, Omenn's Syndrome, Severe Combined means introduce genetic modifications. Such as but not lim Immunodeficiency, Common Variable Immunodeficiency, ited to, the insertion of the TERT gene (telomerase reverse Wiskott-Aldrich Syndrome, X-Linked Lymphoproliferative transcriptase). Cells that have been transfected with vector Disorder. Other Inherited Disorders, Lesch-Nyhan Syn expressing the TERT sequence have become immortal and drome, Cartilage-Hair Hypoplasia, Glanzmann Thrombas can be propagated for an unlimited period of time (PCT thenia, Osteopetrosis, Inherited Platelet Abnormalities, publication WO2005/017117). Amegakaryocytosis, Congenital Thrombocytopenia, Plasma 0145. In one aspect, the invention provides a method for Cell Disorders, Multiple Myeloma, Plasma Cell Leukemia, screening to identify compounds that affect the function of Waldenstrom's Macroglobulinemia, Breast Cancer, Ewing the cells of the invention. In one embodiment, the method Sarcoma, Neuroblastoma, Renal Cell Carcinoma, brain dis includes incubating at least one compound and at least one orders such as Alzheimer's disease, and the like (see, for pluripotent embryonic stem cell expressing DAZL undercon example, hypertext transfer protocol (http) on the worldwide ditions sufficient to allow the compound and cell to interact; web at: marrow. org/index.html, which is incorporated by and determining the effect of the compound on cell function reference herein in its entirety). before and after incubating in the presence of the compound. 0140. Many different types of tissues may be replaced, in Cell function that may be modulated (e.g. inhibited or stimu full or in part, using the differentiated cells derived from the lated) by the compound and includes, but is not limited to, GLSC as described herein. Examples of tissues which may be differentiation, gene expression, production of growth fac (at least partially) replaced include, but are not limited to, tors, response to growth factors and modulation of cell mem lung tissue, heart tissue, ocular tissue, nerve tissue, brain brane permeability. tissue, muscle tissue, skin, pancreatic beta cells, and the like. 0146 Additionally, the fetal stem cells of the present 0141. The isolated cells of the invention may also be invention may be used as autologous/heterologous transgene genetically modified by transfection with any Suitable gene of carriers in genetherapy to correct inborn errors of metabolism interest. General techniques useful to genetically modify the affecting the cardiovascular, respiratory, gastrointestinal, GLSC (or their derivatives) can be found, for example, in reproductive, and nervous systems, or to treat cancer and standard textbooks and reviews in cell biology, tissue culture, other pathological conditions. and embryology. Methods in molecular genetics and genetic 0147 The pluripotent embryonic stem cells of the present engineering are described, for example, in Molecular Clon invention can be used in autologous/heterologous tissue ing: A Laboratory Manual, 2nd Ed. (Sambrook et al., 1989); regeneration/replacement therapy, including but not limited Oligonucleotide Synthesis (M. J. Gait, ed., 1984); Animal to treatment of corneal epithelial defects, cartilage repair, Cell Culture (R.I. Freshney, ed., 1987); the series Methods in facial dermabrasion, burn and wound dressing for traumatic Enzymology (Academic Press, Inc.) Gene Transfer Vectors injuries of skin, mucosal membranes, tympanic membranes, for Mammalian Cells (I. M. Miller & M. P. Calos, eds., 1987); intestinal linings, and neurological structures. For example, US 2008/O 159999 A1 Jul. 3, 2008

augmentation of myocardial performance can be achieved by (FIGS. 1A-I). The culture medium of the present invention is the transplantation of exogenous fetal stem cells into dam Stefanidis medium which comprises about 80% basal aged myocardium, a procedure known as cellular cardiomyo medium 80% KnockCutTM Dulbeco's modified Eagle's plasty (CCM) which can be used for enhancing myocardial performance and treating end-stage cardiac disease. Fetal medium (DMEM) (Gibco BRL, Rockville, Md.), 1 mM stem cells according to the present invention can also be used L-Glutamine, 1% nonessential amino acids Stock (Gibco as a tool for the repair of a number of CNS disorders as BRL, Rockville, Md.), supplemented with 20% KnockCut described in a review by Cao et al. (Stem cell repair of central SRTM, a serum-free replacement originally optimized for nervous system injury, J. Neuroscience Res. 68:501-510, human ES cells (Gibco BRL, Rockville, Md.), penicillin and 2002). The cells of the present invention can also be used in streptomycin, and 20% amniotic fluid supplemented with 4 reconstructive treatment of damaged tissue by Surgical ng/ml basic fibroblast growth factor (bFGF). implantation of cell sheets, disaggregated cells, and cells 0151. The novel culture medium of the invention com embedded in carriers for regeneration of tissues for which prises amniotic fluid and a culture medium as described differentiated cells have been produced. The cells may also be used in tissue engineered constructs. Such constructs com herein. In aspects the medium comprises amniotic fluid and a prise a biocompatible polymer formed into a scaffold suitable growth factor such as but not limited to beta-FGF. for cell growth. The scaffold can be shaped into a heat valve, 0152. After about 96 to about 128 hours or sufficient vessel (tubular), planar construct or any other Suitable shape. period of time to permit a portion of amniotic fluid cells to Such constructs are well known in the art (see, e.g., WO02/ adhere to the Substrate, a non-adhering portion of amniotic 035992, U.S. Pat. Nos. 6,479,064, 6,461,628). The amniotic fluid cells which are believed to mainly contain embryonic fluid, chorionic villus, placenta tissue and embryonic stem like stem cells such as GLSC in the supernatant medium were cells, before or after differentiation, may be cryopreserved in collected. The non-adherent cells then were at 800-1000 rpm a cryoprotective solution comprising a medium or buffer and and plated ina) 5 ml of Stefanidis medium in 25 cm flaskand a cryoprotective agent. Examples of media are Dulbecco's incubated at 37° C. with 5% humidified CO. The cells were Modified Eagle Medium (DMEM), Medium 199 (M199), cultured with replacement of Stefanidis medium every 2-3 F-12 Medium, and RPMI Medium. An example of a buffer is days until cells morphology consistent with EG cells were phosphate buffered saline (PBS). Examples of cryoprotective observed, typically, 10-30 days. On the 20th day of culture, a agents are dimethylsulfoxide (DMSO) and glycerol. subset of cells growing on the 96-well culture dish were fixed Examples of cryoprotective solutions are: DMEM/glycerol and stained for the presence of alkaline phosphatase by using (1:1), DMEM/7.5% DMSO, M199/7.5% DMSO, and PBS/ a commercially available diagnostic kit (Sigma Chemicals, 3.5 M DMSO. Optionally, the samples may be treated with antibiotics such as penicillin or streptomycin prior to cryo product number 86-R). The cells were washed 2 times with preservation. Cryopreservation may be accomplished using a phosphate buffered saline (PBS) then fixed for 30 seconds in rapid, flash-freeze method or by more conventional con a mixture of 25 ml citrate solution (18 mM sodium citrate, 9 trolled rate-freeze methods. Rapid freezing of amniotic tissue mM sodium chloride, pH3.6), 65 ml acetone and 8ml of 37% may be accomplished by placing sample(s) in a freezing tube formaldehyde. Fixed cells were then incubated in the dark for containing a cryoprotective solution and then rapidly immers 15 min. in alkaline-dye mixture. The cells were then rinsed ing the freezing tube in liquid nitrogen. General slow freezing with deionized water for 2 min. and allowed to dry. Alkaline may be accomplished by placing sample(s) in a freezing tube phosphatase positive primordial germ cell (PGC) and EG containing a cryoprotective solution and then placing the cells stained red, while cells that lack alkaline phosphatase freezing tube in a -70.degree. C. freezer. Alternatively, the activity, Such as human fibroblasts, remained clear. sample(s) may be subjected to controlled rate freezing using 0153 Cells were photographed throughout the initial 20 a standard cryogenic rate controlled system. Products of the days of culture using phase contrast microscopy and selected stem cells of the present invention may be used in reconstruc cells were processed for alkaline phosphatase staining as tive treatment, either in vivo or ex vivo. Examples of agents described herein. Cells were also photographed using elec that can be produced using fetal stem cells of the present tron microscopy. invention include growth factors, cytokines, and other bio 0154 It will be appreciated by those of skill in the art that logical response modifiers. should the non-adherent portion of embryonic like stem cells 0148 All references cited herein are hereby incorporated by reference in their entirety. Nothing herein is to be con and germline-like stem cells not be removed after about Strued as an admission that the invention is not entitled to 96-128 hours, these embryonic like stem cells and germline antedate such disclosure by virtue of prior invention. like stem cells may attach to the fibroblast layer formed from Throughout this description, the examples shown should be the mesenchymal adherent population of cells present in the considered as exemplars, rather than as limitations on the amniotic fluid as clearly shown in FIG.1F. present invention. Since modification of the specific embodi ments will be apparent to those of skill in the art, it is intended Example 2 that this invention be limited only by the spirit and scope of the appended claims. Morphological Characterization GLSCs EXAMPLES 0155 Cultured amniotic fluid-derived cells were karyo 0149. In the examples the term “GLSC' is used to refer to typed using methods well known to those in the art. These the novel pluripotent embryonic stem cell of the invention cells could be passaged for at least 5-10 times and were found that expresses DAZL. to be near-immortal and were named germline-like stem cells (GLSC). Example 1 0156 All of 50 amniotic fluid sample harvests of 5 ml gave Amniotic Fluid Cell Isolation and Expansion of rise to at least one adherent GLSC colony and continuous GLSCs in Cell Culture culture. The GLSCs were cloneable into single cell clones 0150 Human AFCs sample were collected and plated in a and were non-senescing. The majority of sample harvests 75 cm flaskand incubated at 37° C. with 5% humidified CO, gave rise to 3-4 individual clones. Among the individual US 2008/O 159999 A1 Jul. 3, 2008

clones, different colonies/cultures had diverse colony mor at list mode data using CellOuest software (Becton Dickin phologies. Some colonies were adherent while other colonies son). Samples were analysed using CellOuest Software. were floating. About half of the amniotic fluid samples cul 0.165 Initially, two main cell subpopulations, R1 and R2, tured under condition A (Stefanidis medium) gave rise to were distinguished according to their forward and side scatter GLSC clones/cultures that behaved like immortal cell lines, characteristics (FIG. 5A). Although both populations autof as shown in FIGS. 2A and 2B, while the other half were luorescenced, the second, R2 population that represented the fibroblasts and differentiated cell types. larger cells, showed an extremely high degree of autofluores 0157. In embodiments of the invention, some GLSCs may cence that interfered with the results (FIGS. 5C and 5D). be differentiated into fibroblasts and have a typical fibroblas Trypan blue viability test was performed in amniotic fluid tic morphology (FIGS. 3A-C). samples to estimate the percentage of dead cells. Almost half 0158. The GLSC cultures grew vigorously, with a dou of the cells were found to be dead (49.64%). These results bling time of 28-34 hours. could not be confirmed by 7AAD staining because of autof 0159. When confluent, the cells piled up in multilayered luorescence interference. However, it is believed that cells in fashion and numerous round, semi-detached cells grew on top the R2 gate mostly represent the dead cell population. of a swirling, non-contact-inhibited layer of cells. These 0166 Thus, the assessment of DAZL and c-kit expression GLSC cultures expressed the telomerase gene/protein. The was performed from the R1 gated cells. All samples including techniques used to determine telomerase activity are common the isotype controls were stained with the dead cell marker and well known to those skilled in the art (N. W. Kim, et al. 7AAD and only 7AAD cells were then selected for further Science 266 (1994), pp. 2011-2015; S. L. Weinrich, et al Nat analysis (FIG.5B). The expression of the surface markers was Genet 17 (1997), pp. 498-502. then assessed as the percentage of positive cells of the 7AAD 0160. Furthermore, the GLSCs were photographed using cell population by Subtracting their expression of their iso electron microscopy as shown in FIGS. 4A-B. Shown in FIG. type controls (Table 2). As can be seen in Table 2, of the cells 4A is a GLSC under electron microscopy and in FIG. 4B is an in this 7AAD- population 34.18% expressed DAZL and embryoid body formed from a GLSC line. 21.73% expressed c-Kit. 0161 The GLSCs vigorously grew and the GLSC lines expressed very high levels of a set of cell surface determinants Example 4 known to be present on undifferentiated embryonic stem cells as explained below. Cell Surface Markers on GLSCs (0167 GLSC expressed very high levels of a set of cell Example 3 Surface determinants known to be present on non-differenti ated human Embryo StemCells (hES) and expressed a set of FACS Analysis of GLSCs surface determinants known to be associated with non-differ 0162 Fresh amniotic fluid cells from 3 donors were pre entiated human Mesenchymal StemCells (MSC). GLSC did pared for FACS analysis by the following protocol: Amniotic not express markers characteristic of hematopoietic cells, e.g. Fluid samples were stained with 3 surface markers/tube. Each CD45 and CD34. The flow cytometry was performed as time two tubes were analyzed, one isotype control or an described above in Example 3. unstained sample and one with the antibodies. The analysis 0168 Mass cultures of the GLSC were characterized by includes the percentages of the cells that express each marker. very high expression of DAZL, SSEA-4, c-Kit, and of the 0163 Amniotic fluid samples were obtained from amnio keratin sulphate-related antigens Tra-1-60 and Tra-1-81 as centesis all performed after the 18 week of pregnancy for shown in FIG. 6. routine prenatal diagnosis. Freshamniotic fluid samples were 0169. The GLSCs also expressed the transcription factor analyzed within 6 hours of collection. Cells were washed OCT-4. The human embryonic stem cell markers typically twice with washing buffer (phosphate buffered saline (PBS), found on GLSC are shown in Table 1. From each amniocen bovine serumalbumin (BSA; 0.1%) and sodium azide (NaN: tesis sample, at least 2-10 colonies that express Oct-4, SSEA 0.1%)) and stained with antibody to c-kit conjugated to phy 4. TRA-1-81 could be achieved. The GLSCs also expressed coerythrin (PE) fluorochrome, 7-Amino-Actinomycin oxytocin receptor. Colony formation was prevented when the (7AAD) and to DAZL indirectly conjugated to fluoresecin oxytocin receptor was blocked using an oxytocin antagonist, isothiocyanate (FITC) (Table 1). Labeled cells were then atociban. washed and resuspended in parafolmadehyde (PFA; 1%) and kept in the dark at 4°C. until acquisition. Fluorochromes Example 5 FITC and PE, and 7AAD were detected by flow cytometric RNA Extraction and RT-PCR analysis as fluorescence 1, 2 and 3, respectively. Mouse monoclonal antibody against c-kit-PE and its isotype control (0170 Total RNA was extracted from approximately were purchased from Abcam (Cambridge, UK); goat poly 3x10 germline like stem cells and 1x10' freshamniotic fluid clonal antibody against DAZL, its secondary donkey anti cells by employing a commercially available kit (RNAeasy goat IgG-FITC antibody and isotype control were obtained micro kit; Qiagen, Valencia, Calif., USA) according to manu from Santa Cruz, Biotechnology Inc.; and 7AAD was pur facturer's instructions. The use of RNase-free DNase I and chased from Becton Dickinson Biosciences. carrier RNA, offered highly purified RNA. 0164. Acquisition of samples was performed with FAC 0171 Total RNA from germline like stem cells and fresh Sort cytometer (Becton Dickinson). The instrument was set amniotic fluid cells were used for cDNA synthesis by reverse for three-colour analysis using CaliBRITE beads (Becton transcription (RT). For the RT reaction a commercially avail Dickinson) with FSC PMT gain on 0.1 (Log) to visualize all able kit was employed (Retroscript kit, Ambion, Austin,Tex. cells, on the FSC vs. SSC dot plot (FIG. 5). Between 20,000 USA). Reverse transcription was followed by two rounds of and 30,000 events were collected for each sample and stored nested PCR for Oct-4 mRNA and by one round of PCR for US 2008/O 159999 A1 Jul. 3, 2008

DAZL mRNA. Primersequences used in PCRs for DAZL and entiation paths GLSC were cultured, and were differentiated Oct-4 mRNA amplification were designed with the Primer 3 into various cell types, such as neural cells, adipogenic cells, program (Rosen and Skaletsy, 1997). All primers were and chondrogenic cells. ordered from MWG Biotech (Table 3). The first round PCR (0176). As shown in FIGS. 8A and 8B, GLSCs may be mastermix contained 3 ul cDNA of Oct-4 in a total 50 ul differentiated into neural glial cells and express the neuro volume. Five ul of 10xPCR buffer, 1.5 mmol MgCl/l, 0.2 markers-100. umol of 3' and 5' outer primer, 0.2 mmol of each dNTP/1 and 1.5 u Taq polymerase were used (Invitrogen Life Technolo Example 8 gies). All reactions were overlaid with light white oil. Poly merase chain reaction was performed for 30 cycles. Cycling Differentiation of GLSC into Spermatogenesis-Like conditions were 94° C. denaturation, 55° C. annealing and Structures 72° C. extension, with each step lasting 1 minute. Reaction was terminated at 72° C. for 10 minute. First round PCR 0177 Both human and mouse embryonic stem cells are products were stored at -20°C. For the second PCR round, 3 capable of forming primordial germ cell in vitro (Kehler, J. ul of the first round PCR product were added to 47 ul of Seminars in Reproductive Medicine 23:222-233, 2005). freshly prepared mastermix containing PCR buffer, MgCl, These germ cells are capable of undergoing meiosis and dNTPs, Taq polymerase and inner primers in the same quan forming both male and female gametes by gametogenesis in tities as the first round. The cycling conditions were also the vitro. For example, GLSCs may be differentiated to sper same as in the first round PCR. matogonia in a testicular environment by a) transplantation in Xenogenic testes and b) in vitro culture using retinoic acid (0172 For DAZL the PCR reaction mixture contained 5ul (RA) at about a final concentration of 10 M. GLSCs of the cDNA in a total volume of 50 ul. The concentrations of PCR present invention are to be differentiated into male gametes buffer, MgCl, dNTPs, Taq polymerase and DAZL specific according to the following method as outlined by Navernia K. primers were the same as in the PCR reaction mixture of et al. Dev. Cell; 11(1):125-32, 2006, where mouse embryonic Oct-4. Polymerase chain reaction was performed for 45 stem cell line R1 (XY) was cultured in an undifferentiated cycles and the cycling conditions were the same as described state on a feeder layer of mitomycin C-inactivated mouse above. Products were stored at -20°C. embryonic fibroblasts with Dulbecco's modified Eagle's 0173 The amplified products were analyzed by electro medium (DMEM, GIBCO-BRL) supplemented with 15% phoresis on 2% agarose gel containing ethidium bromide. FCS, 2 mM L-glutamine (GIBCO-BRL), 50 uM B-mercap Seven ul of each PCR product run in parallel with a 100 bp toethanol (B-ME: Promega), 1x non essential amino acids DNA ladder (Invitrogen Life Technologies). As shown in (NEM; GIBCO-BRL), and 103 U/ml LIF as described previ FIG. 7A, both the fetal amniotic fluid cells (FAFC) and the ously. Linearized plasmid DNA (30 lug) was electroporated GLSCs express DAZL. As shown in FIG. 7B both the fetal into ES cells. Colonies resistant to G418 (400 g/ml) were amniotic fluid cells (FAFC) and the GLSCs express Oct3/4. selected. Resistant colonies were tested by PCR, and colonies that contain the Stra8-EGFP construct were selected and cul Example 6 tured in an undifferentiated state. Cultures were proliferated in the above described medium for an additional 2 months Cryopreservation and Banking of Fresh Amniocente (four passages) and were then frozen. Thereafter, cells were sis-Derived Cells and of Cultured GLSC cultured on a feeder layer of mitomycin C-inactivated mouse 0174 Both freshamniocentesis-derived cells and cultured embryonic fibroblasts with basic ES cell medium. To induce GLSC were cryopreserved for banking purposes. Techniques differentiation, medium was changed to medium containing for cryopreservation are well known and practiced by those of retinoic acid (RA) at a final concentration of 10M, and the skill in the art as disclosed in PCT publication cells were cultured for 10 days. Positive cells (60%) were WO2005017117. Briefly, samples of amniotic fluid ranging sorted by FACS. Briefly, cells were dissociated with 0.25% from 2 to 5 ml were harvested. The cells were centrifuged to trypsin/EDTA, neutralized with DMEM with 10% FCS, remove excess amniotic fluid. The cells were then frozen in washed twice with PBS, and then resuspended in PBS con medium containing 10% dimethyl sulfoxide and 25% fresh, taining 0.5% BSA. Approximately 2x10 cells/ml in PBS/ filtered (0.10 micron) amniotic fluid (DMSO/AF freezing BSA were used for sorting. The flow cytometry was per medium). Alternatively, the cells were grown to produce formed on a FAC-Star Plus (Becton Dickinson) equipped GLSC cultures, which were then frozen. The fresh amniotic with dual 488 nm argon and 633 nm helium neon lasers. fluid derived cells and cultured GLSCs were frozen in Sorted cells were cultured in RA-free medium. After 8-10 DMSO/amniotic fluid freezing medium in a controlled-rate weeks (4 passages), medium was changed with medium liquid nitrogen freezer at 1° C./min to about 10° C./min. supplemented with RA (10-6M) and after 12 h, GFP positive Frozen samples were stored under liquid nitrogen in freezing cells (90%) were sorted by FACS. Thereafter, the cells were ampoules. cultured in basic medium supplemented with LIF on fibro blast feeder layers and transfected with the Prm1-DsRed con Example 7 struct. Positive cells colonies were selected after PCR analy sis. Two cell lines were established and designated as SSC7 Differentiation of GLSCs and SSC12. For differentiation, the cells were cultured on gelatine-coated dishes, without LIF. The cells were charac 0.175. As mentioned previously, the GLSCs may be differ terized by determining the expression of different markers for entiated into many cell types. For example, GLSCs cells can PGCs, premeiotic, meiotic, and postmeiotic male germ cells be differentiated into cells of ectoderm, mesoderm and endo by RT-PCR analysis. To investigate SSC capacity and the derm. In addition to the differentiation paths exemplified further development of SSC7 and SSC12 cell lines in vivo, below, GLSCs cells are capable of other, pluripotent differ cells were transplanted into one of the testes of germ cell US 2008/O 159999 A1 Jul. 3, 2008

depleted recipient mice. The other testis served as an internal Scan ArrayTM Lite (PerkinElmer Life Sciences). Shown in control. Histological analysis of testes after 4 months showed FIG. 9 is a false colour image of the microarray experiment is the appearance of spermatogenesis-like-structures and sperm shown: Red colour indicates that the Cy5 signal intensity is in the lumen of two of ten transplanted mice (for further higher than the Cy3 signal intensity. Therefore, the corre details please refer to the relevant article.) sponding gene is overexpressed in the Experimental sample. Green spots, however, indicate that the fluorescence intensity Example 9 in the control sample is stronger than in the experimental sample. Yellow spots indicate that the signal intensities are Comparison of Gene Expression Profiles Between equal for both samples. Spots located in areas in which Amniotic Fluid Cells Cultured in Stefanidis Medium hybridization artefacts such as air bubbles occur, are flagged and Germ Cells from 18-20 Week Embryos and excluded from further analysis. Even if one or two spots 0.178 Gene expression profiles between amniotic fluid are flagged, Sufficient replicates for valid data analysis remain cell Samples (obtained for routine prenatal diagnostic amnio on the slide since each gene is spotted on four different centesis after the 18th week of pregnancy) were cultured with positions on the microarray. Stefanidis medium according the present invention (Control 0183 Mean signal and mean local background intensities cells) and cells derived from human gonadal ridges and dorsal were obtained for each spot of the microarray images using mesenteries (primordial germ cells) from 18th-20th week old the ImaGene software (Biodiscovery). The PIQORTM Ana embryos (from an aborted pregnancy due to Down syndrome) lyZer allows automated data processing of the raw data text (Experimental cells) were compared using DNA microarray files derived from the ImaCiene software. This includes back analysis. ground subtraction to obtain the net signal intensity, data (0179 Cells derived from primordial germ cells (PGCs) are normalization, and calculation of the Cy5/Cy3 ratios. As an termed human embryonic germ cells (EG) cells, can undergo additional quality filtering step, only spots/genes are taken self-renewal in vitro and maintain an undifferentiated pheno into account for the calculation of the Cy5/Cy3 ratio that have type. As described above, DAZL., Oct-4, Nanog, SSEA-4, at least in one channel a signal intensity that is at least 2-fold SSEA-1 represent characteristic markers of human EG cells. higher than the mean background. The result of this data DAZL belongs to DAZ gene family which is expressed in analysis is visualized in a doublelog scatter plot (FIG. 10): prenatal and postnatal germ cells of males and females. Oct-4 0.184 As seen in the scatter plot above the vast majority of POU transcription factor is expressed in totipotent embryonic the genes examined share similar expression patterns in stem and germ cells and rapidly disappears when cells differ GLSC and EG cells. entiate. The stage-specific embryonic antigen 4 (SSEA4) is 0185 PIOORTM Analyzer calculates all normalized mean expressed in undifferentiated human ES cells and is down Cy5/Cy3 ratios of the four replicates per gene (Table 4). In regulated during differentiation, while SSEA1 is expressed addition to the ratio, the respective coefficient of variation (cv, only in later stages of human ES cells differentiation. in %) is listed in the generatio list. This coefficient of varia 0180 Expression of DAZL., Oct-4, Nanog, SSEA-4, tion refers to the average of the Cy5/Cy3 ratios for the gene SSEA-1 in Control and Experimental cells was assessed by replicates. However, a negative value (-%) indicates that only semiquantitative RT-PCR and immunofluorescence (IF) one out of four spots could be evaluated and, therefore, no cv analysis. It was determined that that both amniotic fluid stem could be determined. cells (cultured according to the composition and methods of 0186 Genes that are >1.7-fold up- or downregulated rep the present invention) and human embryonic germ cells posi resent putative candidate genes and are highlighted by green tively expressed similar levels of DAZL., Oct-4, Nanog, and red color in the generatio list. Green colour indicates a SSEA-4. Interestingly embryonic germ cells were found <0.58-fold down-regulation of gene expression in Experi negative for SSEA-1 which underlines their undifferentiated mental Cells (Germ cells from Down Syndrome), corre status and strengthens the evidence for their germ cell iden sponding to a fold change <-1.7 of a certain gene in compari tity. Considering their origin from 18-20 week embryos, it son to the Control sample (Amniotic fluid stem cells). Red should be expected to positively express SSEA-1, but Down colour indicates a more than 1.7-fold up-regulation of the syndrome has been reported to associate with delayed respective gene in comparison to the control (Amniotic fluid gonadal maturation, therefore explaining the absence of stem cells). The cells of spots/genes that did not pass the SSEA-1. quality filtering because they are either flagged or have very 0181. To further investigate the similarities in gene expres low signal intensities are blanked in Table 4, in order to sion between germ cells and amniotic fluid stem cells, two discriminate questionable results from relevant results in the vials containing the human cell samples kept under dry ice generatio list. were provided. RNA was isolated using standard RNA 0187. Of all the 937 spots/genes that passed the quality extraction protocols (NucleoSpinTM RNA II, Macherey-Na filtering 80 (i.e. 8.5%) were found up-regulated and 57 (i.e. gel). The gene expression was assessed using the PIOOR 6.1%) were found down-regulated in germ cell line compared microarray, as briefly described: to amniotic fluid stem cells. Genes that were found differen 0182 Sample labelling was performed according to the tially expressed between the two examined cell lines, mostly PIQORTM User manual. Subsequently, the fluorescently associate with formation of cytoskeleton and adhesion to their labelled samples were hybridized overnight to topic-defined surrounding matrix (such as VCAM1, ALCAM, ITGB1, PIQORTM StemCell Microarrays Human Antisense using the ITGA1 2, COL1A1, COL18A1 2, COL2A1, TIMP3, a-HybTM Hybridization Station. In general, Control samples LAMA1, FN1, MMP16 1, KRT18, KRT8, TPM1, FN1 (Amniotic Fluid stem cells) are labeled with Cy3 and Experi REPEAT-1TO6, FN1 REPEAT-A, FN1 REPEAT-B, mental samples (Germ cells from Down Syndrome) are MMP21-22-23), communication with their microenviron labeled with Cy5. Fluorescence signals of the hybridized ment (such as EDN1, VEGC, HTR2B, EDNRB, HBEGF, PIQORTM Microarrays were detected using the laser scanner FGF5, VEGFA, VGR1, IGFBP2, IGFBP5), regulation of cell US 2008/O 159999 A1 Jul. 3, 2008 14 cycle and proliferation (such as CCNB2, CCNE1, MAPK3, cells. Dev Dyn. 2005 February; 232(2):487-97.) are consid CXCR4, CDK4, CDC25C, MAPK13, C20ORF1, MAD2L1, ered to be “core stemness genes, because they are found BUB1B, BUB3, MAD2L2, REC1) and immune response overexpressed in almost all stem cell lines. (IL6, CD9, CXCL12, PGH2). These differences respectively, (0189 GABRB3 (GABRB3, GABA A receptor, b3) could be attributed to the differential origin of the donor (Sperger, J. M. et al. Gene expression patterns in human Subjects (different human donors), to specific adaptation embryonic stem cells and human pluripotent germ cell mechanisms of the progenitor cells in their original microen tumors. Proc. Natl. Acad. Sci. USA 100, 13350-13355, Vironment, differences in cell cycle regulation and prolifera 2003), FGF4 (International Stem Cell Initiative, Character tion potential since amniotic fluid cells are known to prolif ization of human embryonic stem cell lines by the Interna erate slower, and possible contamination of the original tional StemCell Initiative. Nat Biotechnol. 2007 July; 25(7): sample (especially the germ cells from obtained from embry 803-16) and TERT (Li SS, Liu Y H, Tseng CN, Chung TL, onic testis) with immune system elements during the isolation Lee TY, Singh S Characterization and gene expression pro process. filing of five new human embryonic stem cell lines derived in 0188 POU5F1 encoding OCT3/4, TDGF, GABRB3, Taiwan. Stem Cells Dev. 2006 August; 15(4):532–55) are FGF4, and TERT represent genes particularly known to be also represent stemness-related genes. FGF4 is a downstream expressed in stem cells and germ cells become down-regu target of the FGF (Fibroblast Growth factor) cascade and lated upon differentiation. Among them POU5F1 (Nichols, J. downregulated upon stem cells differentiation. TERT is et al. Formation of pluripotent stem cells in the mammalian related to telomerase function and telomeres maintenance embryo depends on the POU transcription factor OCT4. Cell during stem cells renewal. 95, 379–391, 1998), Nanog (Mitsui, K. et al. The homeopro 0190. Importantly, the DNA microarray analysis revealed tein Nanog is required for maintenance of pluripotency in that many other genes not previously examined with RT-PCR mouse epiblast and ES cells. Cell 113, 631-642, 2003, Cham or IF, were found to be equally expressed between the two bers, I. etal. Functional expression cloning of Nanog, a pluri types of cells, namely, the GLSCs and the human embryonic potency Sustaining factor in embryonic stem cells. Cell 113, germ cells. These are POU5F1, TDGF, GABRB3, FGF4 and 643-655, 2003), TDGFTeratocarcinoma-derived growth fac TERT. POU5F1 and TDGF. These genes are commonly tor-1 (Sato N, Sanjuan I M, Heke M, Uchida M, Naef F, known to associate with pluripotency and they become Brivanlou A. H. Molecular signature of human embryonic strongly downregulated upon differentiation of stem cells, stem cells and its comparison with the mouse. Dev Biol. 2003 providing reliable stem cell markers. Aug. 15: 260(2):404-13, Baldassarre, G. et al. Transfection 0191 Conclusively, the results suggest that amniotic fluid with a CRIPTO anti-sense plasmid suppresses endogenous cells cultured according to the composition and methods of CRIPTO expression and inhibits transformation in a human the present invention, specifically the GLSCs and human embryonal carcinoma cell line. Int. J. Cancer 66, 538-543, embryonic germ cells share common expression patterns, 1996, Sperger, J. M. et al. Gene expression patterns in human particularly for genes associated with undifferentiated pluri embryonic stem cells and human pluripotent germ cell potent status of embryonic stem and embryonic germ cells. tumors. Proc. Natl. Acad. Sci. USA 100, 13350-13355, 2003, 0.192 The above-described embodiments are intended to Gerecht-Nir S, Dazard J. E. Golan-Mashiach M. Osenberg S. be examples of the present invention and alterations and Botvinnik A, Amariglio N. Domany E. Rechavi G. Givol D, modifications may be effected thereto, by those of skill in the Itskovitz-Eldor J. Vascular gene expression and phenotypic art, without departing from the scope of the invention which correlation during differentiation of human embryonic stem is defined solely by the claims appended hereto.

TABLE 1

Purified Antibody Secondary Isotype Applications Company c-kit-PE PE-conjugated Flow cytometry abcam Mouse monoclonal mouse IgG1 (ab11290) isotype control (ab18429) Oct.-3,4-PE Rat IgG2B Flow cytometry R&D Monoclonal (ICO13P) (IC1759) SSE1-PE gM-PE Flow cytometry Santa Cruz (sc-21702) (sc-2870) SSEA-4 (813-70) Goat-anti-mouse-FITC Normal Flow cytometry Santa Cruz (sc-21704) (sc2081) Mouse IgG3 FITC (sc-2858) DAZL (Y-15) donkey anti-goat IgG- Goat IgG- Flow cytometry Santa Cruz Goat FITC FITC polyclonal (sc-2024) (sc-3988) (sc-27332) Tra-1-81 Goat anti-mouse IgM- Normal mouse Flow cytometry Santa Cruz Mouse FITC gM-FITC monoclonal (sc-2082) (sc-2859) (sc-21706) US 2008/O 159999 A1 Jul. 3, 2008 15

TABLE 1-continued

Purified Antibody Secondary Isotype Applications Company FcR Blocking reagent Blocks FcRs MACS (130 059901)

TABLE 2 % pos. cells STDEV c-kit 21.73 1.99 DAZL 34.18 8.17

TABLE 3 Annealing Temperature Product mRNA Primers 5'-3' Sequence (o C.) size

DAZL forward CCA CCA CAG TTT CAG AAT GTC 55 593 (SEQ ID No: 1)

reverse CAA AGT TTG. AGT, GTG ATT TAC CA 55 (SEQ ID No: 2)

Oct - 4 forward outer GAG GAA GCT GAC AAC AAT GAA 55 249 (SEQ ID No : 3)

reverse oute GGT TTT CTT. TCC CTA GCT CCT 55 (SEQ ID No.: 4)

forward inner CAG GAG ATA TGC AAA GCA GAA 55 (SEQ ID No. 5)

reverse inner AGC CTC AAA ATC CTC TCG TT 55 (SEQ ID No.: 6)

TABLE 4 Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 43 TNFR1: (TNFRSF1A OR TNFR1 ORTNFAR P19438 NM OO1065 O.76.10% ORTNFR-1) TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILYMEMBER 1A PRECURSOR (TUMOR NECROSIS FACTOR RECEPTOR 1) (TUMOR NECROSIS FACTOR BINDING PROTEIN 1) (TBPI) (P60) (TNF-R1) (TNF-RI) (P55) (CD120A). 47 ACTA2: (ACTA2 ORACTSA ORACTVS) P62736 NM OO1613 O.62.12% AORTICSMOOTH MUSCLE (ALPHA-ACTIN 2). 49 TUBA HUMAN: ((TUBA1B) AND (TUBA1A) P68363 NM OO6009 1.52.12% AND (TUBA1C)) TUBULIN ALPHA- Q9BQE3 NM OO6082 UBIQUITOUS CHAIN (ALPHA-TUBULIN Q71U36 NM 032704 UBIQUITOUS) (TUBULINK-ALPHA-1) NR OO3063 (TUBA6) (TUBULIN ALPHA-6 CHAIN) (ALPHA-TUBULIN 6) (TUBA3) (TUBULIN ALPHA-3 CHAIN) (ALPHA-TUBULIN3) (TUBULIN B-ALPHA-1). 55 TUBB HUMAN: (TUBB ORTUBB5) PO7437 NM 178O14 TUBULIN BETA CHAIN (TUBULIN BETA-5 CHAIN). 67 BRCA1: (BRCA1 OR RNF53) BREAST P38398 NM OO7294 CANCERTYPE 1 SUSCEPTIBILITY NM OO7295 PROTEIN (RING FINGER PROTEIN 53). NM OO7296 NM OO7297 US 2008/O 159999 A1 Jul. 3, 2008 16

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 NM OO7298 NM OO7299 NM O 87 CD KN1A: (CDKN1A ORCDKN1 ORCIP1 OR Q9BUT4 NM 000389 O.69.9% WA F1 ORMDA6 OR SDI1 ORPIC1 OR P38.936 Q14010 NM O78467 CA P20) CYCLIN-DEPENDENT KINASE INH IBITOR1 (MELANOMA DIF FERENTIATIONASSOCIATED PROTEIN 6) (MDA-6) (P21) (CDK-INTERACTING PROTEIN 1). 89 CDKN1B: (CDKN1B ORKIP1) CYCLIN Q9BUS6 NM 004.064 DEPENDENT KINASE INHIBITOR 1B P46527 Q16307 (CYCLIN-DEPENDENT KINASE INHIBITOR P27) (P27KIP1). 91 : (TP53 ORP53) CELLULARTUMOR Q15086 Q15088 NM 000546 1.04.20% ANTIGEN P53 (TUMOR SUPPRESSORP53) Q16535 Q16807 (PH OSPHOPROTEIN P53). Q16808 Q16809 Q16810 Q16811 Q86UG1 Q 106 TNFSF11: (TNFSF11 OR RANKL OR Q9P2Q3 NM 003701 TRANCE OR OPGL) TUMOR NECROSIS O14788 O14723 NM 033012 FACTOR LIGAND SUPERFAMILYMEMBER 11 (RECEPTORACTIVATOR OF NUCLEAR FACTOR KAPPA BLIGAND) (RANKL) (TNF RELATED ACTIVATION-INDUCED CYTOKINE) (TRANCE) (OSTEOPROTEGERIN LIGAND) (OPGL) (OSTEOCLAST D 118 CCNB2: (CCNB2) CYCLIN B2G2/MITOTIC O95067 NM 004701 SPECIFIC CYCLIN B2. 120 CCNC 1: (CCNC) CYCLIN C. P24863 Q9H543 NM 00101.3399 1.13.22% NM 005190 128 CCNE 1: (CCNE1 ORCCNE) CYCLINE G1/S NM OO1238 SPECIFIC CYCLINE1. NM 057182 134 CCNG2: (CCNG2) CYCLING2. NM 004354 138 CCNE2: (CCNE2) G1/S-SPECIFICCYCLIN E2. NM 004702 NM 057735 NM O57749 139 MAPK3: (MAPK3 OR PRKM3 OR ERK1) P27361 NM OO2746 MITOGEN-ACTIVATED PROTEINKINASE 3 (EC 2.7.1. ) (EXTRACELLULAR SIGNAL REGULATED KINASE 1) (ERK-1) (INSULIN STIMULATED MAP2 KINASE) (MAP KINASE 1) (MAPK1) (P44-ERK1) (ERT2) (P44 MAPK) (MICROTUBULE-ASSOCIATED PROTEIN-2 KINAS 143 MA PK6: (MAPK6 OR PRKM6 OR ERK3) NM OO2748 MITOGEN-ACTIVATED PROTEINKINASE 6 2.7.1. ) (EXTRACELLULAR SIGNAL REGULATED KINASE 3) (ERK3) (P55 K). 149 K12: (MAPK12 OR SAPK3) MITOGEN P53778 Q14260 NM OO2969 1.03.8% TIVATED PROTEINKINASE 12 Q99588 Q99672 (EXTRACELLULAR SIGNAL-REGULATED KINASE 6) (EC 2.7.1. ) (ERK6) (STRESS ACT CIVATED PROTEIN KINASE-3) (MITOGEN-ACTIVATED PROTEIN KINASE P38 GAMMA) (MAP KINASE P38 GAMMA). 163 MA PK14: (MAPK14 ORCSBP1 ORCSBP2 OR Q16539 Q14084 NM 001315 0.94.43% CSBP ORMXI2) MITOGEN-ACTIVATED Q13083 O60776 NM 139012 PROTEIN KINASE 14 (EC 2.7.1.37) Q8TDXO NM 139013 (MITOGEN-ACTIVATED PROTEIN KINASE NM 139014 P38ALPHA) (MAPKINASE P38ALPHA) (CYTOKINE SUPPRESSIVE ANTI LAMMATORY DRUGBINDING PROTEIN) (CSAID BINDING PROTEIN) (C 16S MA PK11: (MAPK11 OR PRKM11 ORSAPK2) O15472 Q15759 NM 002751 O.79.52% MITOGEN-ACTIVATED PROTEINKINASE OOO284 NM 138993 1 ( EC 2.7.1.37) (MITOGEN-ACTIVATED Q2XNF2 PROTEIN KINASE P38 BETA) (MAPKINASE P38 BETA) (P38B) (P38-2) (STRESS ACT CIVATED PROTEIN KINASE-2). US 2008/O 159999 A1 Jul. 3, 2008 17

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 211 CASP8 1: (MCH5 OR CASP8) CASPASE 8 NM OO1228 PRECURSOR (EC 3.4.22. ) (ICE-LIKE NM 03.3355 APOPTOTIC PROTEASE 5) (MORT1 NM 03.3356 ASSOCIATED CED-3 HOMOLOG) (MACH) (FADD HOMOLOGOUS ICE/CED-3-LIKE PROTEASE) (FLICE) (APOPTOTIC CYSTEINE PROTEASE) (APOPTOTIC PROTEASE MCH-5) (CAP4). 234 NGFR: (NGFRORTNFRSF16) LOW NM OO2507 1.05.20% AFFINITYNERVE GROWTH FACTOR RECEPTOR PRECURSOR (NGF RECEPTOR) (GP80-LNGFR) (P75 ICD) (LOWAFFINITY NEUROTROPHIN RECEPTORP75NTR) (CD271 ANTIGEN). 241 TNFSF4: (TNFSF4 ORTXGP1) OX40 LIGAND NM OO3326 (OX4OL) (GLYCOPROTEIN GP34) (TAX TRANSCRIPTIONALLY ACTIVATED GLYCOPROTEIN 1) (CD252ANTIGEN). 251 TNFRSF1B: (TNFRSF1B OR TNFR2 OR NM OO1066 TNFBR OR TNFR-2) TUMORNECROSIS FACTOR RECEPTORSUPERFAMILY MEMBER1B PRECURSOR (TUMOR NECROSIS FACTOR RECEPTOR2) (TUMOR NECROSIS FACTOR BINDING PROTEIN 2) (TBPII) (P80) (TNF-R2) (P75) (CD120B) (ETANERCEPT). 301 CYPA: (PPIA ORCYPA) CYCLOPHILIN 1 NM 021130 PEPTIDYL-PROLYL CIS-TRANS SOMERASEA (EC5.2.1.8) (PPIASE) (ROTAMASE) (CYCLOPHILINA) (CYCLOSPORINA-BINDING PROTEIN). 303 CAM2: (ICAM2 ORICAM-2) Q14600 P13598 NM OOO873 1.17.21% NTERCELLULARADHESIONMOLECULE-2 PRECURSOR(ICAM-2) (CD102) (LYMPHOCYTE FUNCTION-ASSOCIATED AG-1 COUNTER-RECEPTOR). 305 TGAE: (ITGAE) INTEGRIN ALPHA-E NM OO2208 1.21f4% PRECURSOR (MUCOSALLYMPHOCYTE-1 ANTIGEN) (HML-1 ANTIGEN) (CD103 ANTIGEN) (INTEGRIN ALPHA-IEL) (INTEGRIN ALPHAM290). 307 TGB4: (ITGB4) INTEGRIN BETA-4 O15339 O15340 NM 000213 PRECURSOR (GP150) (CD104). O15341 O14691 NM 001005619 Q9UIQ4 NM 001005731 O14690 P16144 309 NG: (ENG OR END) ENDOGLIN Q14926 P17813 NM 000118 RECURSOR (CD105 ANTIGEN) (CELL Q14248 URFACE MJ7/18 ANTIGEN). 311 CAM1: (VCAM1 ORL1CAMORVCAM-1) NM 001078 0.24.66% ASCULAR CELLADHESION PROTEIN 1 P1932O NM 080682 RECURSOR (V-CAM 1) (CD106 ANTIGEN) (INCAM-100). 322 KIT: (KIT ORSL) MAST/STEM CELL P10721 NM 000222 1.20.13% GROWTH FACTOR RECEPTOR PRECURSOR (EC 2.7.1.112) (SCFR) (PROTO-ONCOGENE TYROSINE-PROTEIN KINASE KIT) (C-KIT) (CD117 ANTIGEN) (C-KIT RECEPTOR TYROSINE KINASE). 324 IFNGR1: (IFNGR1 ORIFNGR) INTERFERON P15260 NM 000416 O.S.O.25% GAMMA RECEPTOR ALPHA CHAIN PRECURSOR (CDW119) (CD119). 326 IL1R1: (IL1R1 ORIL1RAORIL1R) P14778 NM OOO877 INTERLEUKIN-1 RECEPTOR, TYPE I PRECURSOR (IL-1R-1) (IL-1R-ALPHA) (P80) (ANTIGEN CD121A). 328 IL1R2: (IL1R2 OR IL1RB) INTERLEUKIN-1 NM 004633 RECEPTOR, TYPE II PRECURSOR(IL-1R-2) NM 173343 (IL-1R-BETA) (ANTIGEN CDW121B). 332 IL3RA: ((IL3RAXORIL3RA OR IL3R OR P26.951 NM 002183 I L3RX) AND (IL3RAY OR IL3RAORIL3ROR I L3RY)) INTERLEUKIN-3 RECEPTOR ALPHACHAIN PRECURSOR(IL-3R-ALPHA) (CD123 ANTIGEN).

US 2008/O 159999 A1 Jul. 3, 2008 19

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 MOLECULE) (ALCAM) (HB2) (KG-CAM) (DM-GRASP PROTEIN). 389 TGAV: (ITGAVORVNRA) VITRONECTIN PO6756 NM OO2210 RECEPTOR ALPHIA SUBUNIT PRECURSOR (INTEGRIN ALPHA-V) (CD51). 397 NCAM1 1: (NCAM1 OR NCAM) NEURAL P13592P13593 NM 000615 CELL ADHESION MOLECULE, 140 KDA Q16180 Q15829 NM 001076682 OFORM PRECURSOR(N-CAM 140) P13591 NM 181351 (NCAM-140) (CD56 ANTIGEN) (NEURAL CELL ADHESION MOLECULE, PHOSPHATIDYLINOSITOL-LINKED SOFORM PRECURSOR) (N-CAM 120) (NCAM-120) (CD56 ANTIGEN) (NEURAL CELL ADHES 399 CD58 HUMAN: (CD58 ORLFA3) Q96KI9 P19256 NM OO1779 LYMPHOCYTEFUNCTION-ASSOCIATED ANTIGEN3 PRECURSOR(AG3) (ANTIGEN CD58) (SURFACE GLYCOPROTEIN LFA-3). 401 TGB3: (ITGB3 OR GP3A). INTEGRIN BETA-3 Q14648 O15495 NM 000212 PRECURSOR (PLATELET MEMBRANE P05106 Q13413 LYCOPROTEIN IIIA) (GPIIIA) (CD61 Q16499 Q12806 TIGEN). 403 LE: (SELE OR ELAM1 OR ELAM-1) E P16581 P16111 NM 000450 ECTIN PRECURSOR (ENDOTHELIAL sEU KOCYTE ADHESIONMOLECULE 1) (ELAM-1) (LEUKOCYTE-ENDOTHELIAL CELL ADHESIONMOLECULE2) (LECAM2) (CD62E). 40S SELL: (SELL ORLYAM1 ORLNHRORLY P14151 P15023 NM OOO655 22) L-SELECTIN PRECURSOR (LYMPH NODE HOMING RECEPTOR) (LEUKOCYTE ADHESIONMOLECULE-1) (LAM-1) (LEUKOCYTE SURFACE ANTIGEN LEU-8) (TQ1) (GP90-MEL) (LEUKOCYTE ENDOTHELLAL CELL ADHESION MOLECULE 1) (LECAM1) (CD62L) (LY-22) 416 CD68: (CD68) MACROSIALIN PRECURSOR NM OO104.0059 0.84-96 (CD68 ANTIGEN) (GP110). NM OO1251 422 TFRC MIDDLE: (TFRC) TRANSFERRIN NM OO3234 1.00 % RECEPTOR PROTEIN (TFR1) (TR) (TFR) (TRFR) (CD71 ANTIGEN) (T9) (P90).

426 NT5: (NTSE OR NTS ORNTE) 5'- NM OO2526 OS 6.13% NUCLEOTIDASE PRECURSOR (EC 3.1.3.5) (ECTO-NUCLEOTIDASE) (5'-NT) (CD73 ANTIGEN). 438 KAI1: (KAI1 OR CD82 OR SAR2) CD82 P27.701 NM 001024844 O.28.10% ANTIGEN (INDUCIBLE MEMBRANE NM OO2231 PROTEINR2) (C33 ANTIGEN) (IA4) (METASTASIS SUPPRESSORKANGAI1) (SUPPRESSOR OF TUMORIGENICITY-6). 446 PLAUR: (PLAUROR UPARORMO3) NM 002659 1.50.7% UROKINASE PLASMINOGENACTIVATOR SURFACE RECEPTOR, GPI-ANCHORED FORM PRECURSOR(U-PAR) (UPAR) (MONOCYTE ACTIVATION ANTIGEN MO3) (CD87 ANTIGEN). 451 THY1: (THY1) THY-1 MEMBRANE NM OO6288 1.141.1% GLYCOPROTEIN PRECURSOR (THY-1 ANTIGEN) (CDW90) (CD90 ANTIGEN). 464 MME: (MME OR EPN) NEPRILYSIN (EC PO8473 NM OOO902 O.73, 90 3.4.24.11) (NEUTRAL ENDOPEPTIDASE) NM OO7287 (NEP) (ENKEPHALINASE) (COMMON NM OO7288 ACUTELYMPHOCYTICLEUKEMIA NM OO7289 ANTIGEN) (CALLA) (NEUTRAL ENDOPEPTIDASE 24.11) (CD10). 466 ITGAL: (ITGAL OR CD11 AORLFA-1) NM OO2209 INTEGRINALPHA-LPRECURSOR (LEUKOCYTE ADHESION GLYCOPROTEIN LFA-1 ALPHACHAIN) (LEUKOCYTE FUNCTIONASSOCIATED MOLECULE 1. US 2008/O 159999 A1 Jul. 3, 2008 20

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 ALPHACHAIN) (CD11A) (INTEGRIN ALPHA-L). 469 ANPEP: (ANPEP OR PEPNORAPN ORCD13 NM 001150 ORLAP1 ORLAP-1) AMINOPEPTIDASEN (EC 3.4.11.2) (MICROSOMAL AMINOPEPTIDASE) (GP150) (MYELOID PLASMA MEMBRAINE GLYCOPROTEIN CD13) (P161 MEMBRANE PROTEIN) (MAPN) (RAPN) (ALANYL AMINOPEPTIDASE) (AMINOPEPTIDASEM) (APM) ( 475 TGB2: (ITGB2 ORCD18) INTEGRIN BETA P05107 Q16418 NM 000211 2 PRECURSOR(CELL SURFACE ADHESION GLYCOPROTEINS LFA-1/CR3/P150,95 BETA-SUBUNIT) (CD18) (COMPLEMENT RECEPTORC3 BETA-SUBUNIT). 489 CD24: (CD24 OR CD24A) SIGNAL Q16257 P25063 NM 013230 O.12.10% TRANSDUCERCD24 PRECURSOR (M1/69 11D HEAT STABLE ANTIGEN) (HSA) (NECTADRIN) (LY-52) (X62 HEAT STABLE ANTIGEN) (R13-AG). 499 TGB1: (ITGB1 ORFNRB). INTEGRIN BETA P78466 P78467 NM 002211 0.49.12% PRECURSOR(FIBRONECTIN RECEPTOR Q13089 Q14647 NM 03.3666 BETA SUBUNIT) (CD29 ANTIGEN) Q13090 Q13212 NM O33667 (INTEGRIN VLA-4 BETA SUBUNIT). Q13091 Q14622 NM 03.3668 P05556 NM 03.3669 NM 133376 PECAM1: (PECAM1 OR PECAM-1 OR NM 000442 PECAM) PLATELET ENDOTHELLAL CELL ADHESIONMOLECULE PRECURSOR (PECAM-1) (CD31 ANTIGEN) (ENDOCAM) (GPIIA).

505 CD33: (CD33) MYELOID CELL SURFACE NM OO1772 ANTIGENCD33 PRECURSOR (GP67) (SIGLEC-3). SO6 CD34: (CD34) HEMATOPOIETIC P28906 Q15970 NM OO1773 1.14.50% PROGENITORCELLANTIGENCD34 Q15971 PRECURSOR 512 CD37: (CD37) LEUKOCYTE ANTIGENCD37. P11049 NM OO1774 O45.15% S1.4 CD38: (CD38) ADP-RIBOSYLCYCLASE 1 Q96HY4 NM OO1775 (EC 3.2.2.5) (CYCLIC ADP-RIBOSE OOO121 OOO122 HYDROLASE 1) (CADPRHYDROLASE 1) P28907 (LYMPHOCYTE DIFFERENTIATION ANTIGENCD38) (T10) (ACUTE LYMPHOBLASTICLEUKEMIA CELLS ANTIGENCD38) (NIM-R5 ANTIGEN) (I-19) (CD38 HOMOLOG) (CD38H 526 ITGA2B: (ITGA2B OR ITGABORGP2B) Q14443 O95366 NM 000419 1.32 % PLATELET MEMBRAINE G LYCOPROTEIN PO8514 IIB PRECURSOR (GPIB) (GPALPHA IIB) (INTEGRIN ALPHA-IIB) (C D41). 538 CD44 EX10-12 HUMAN: (CD44 OR LHR) Q96J24 Q92493 NM 000610 CD44 ANTIGEN PRECURSOR Q13961 Q13967 NM OO1 OO1389 (PHAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q13968 Q13980 (HUTCH-I) (EXTRACELLU LARMATRIX Q15861 Q16064 RECEPTOR-III) (ECMR-III) (GP90 Q16065 Q LYMPHOCYTE HOMING-ADHESION RECEPTOR) (HERMES ANTCIGEN) (HYALURONATE RECEPTOR) (HEPARAN SULFATE PROTE 543 CD47: (CD47 ORLAP) LEUKOCYTE NM 001025079 101.9% SURFACE ANTIGENCD47 PRECURSOR NM 001777 (ANTIGENIC SURFACE DETERMINANT NM 198793 PROTEINOA3) (INTEGRIN ASSOCIATED PROTEIN) (LAP) (MER6) (ITGP) (INTEGRIN ASSOCIATED PROTEIN PRECURSOR). 547 ITGA1 1: (ITGA1) INTEGRIN ALPHA-1 P561.99 NM 1815O1 O.76.22% (LAMININ AND COLLAGEN RECEPTOR) (VLA-1) (CD49A).

US 2008/O 159999 A1 Jul. 3, 2008 22

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 632 CHRM1: (CHRM1) MUSCARINIC P11229 NM OOO738 ACETYLCHOLINE RECEPTORM1. 634 CHRM2: (CHRM2) MUSCARINIC NM OOO739 1.27.4% ACETYLCHOLINE RECEPTORM2. 703 DRD2: (DRD2) D(2) DOPAMINE RECEPTOR NM 000795 NM O16574 705 DRD3: (DRD3) D(3) DOPAMINE RECEPTOR. NM 000796 NM 03.3658 NM 03.3659 NM 03.3660 NM O33663 711 DRD5: (DRD5 OR DRD1B) D(1B) DOPAMINE NM 000798 RECEPTOR (D(5) DOPAMINE RECEPTOR) (D1BETADOPAMINE RECEPTOR). 713 EDNRA: (EDNRAORETRA) ENDOTHELIN-1 NM OO1957 RECEPTOR PRECURSOR (ET-A).

715 E DNRB: (EDNRB OR ETRB) ENDOTHELIN B NM OOO115 RECEPTOR PRECURSOR (ET-B) NM OO3991 (ENDOTHELIN RECEPTOR NON SELECTIVE TYPE). 812 GJA1: (GJA1) GAP JUNCTIONALPHA-1 NM OOO165 1.03.17% PROTEIN (CONNEXIN 43) (CX43) (GAP JUNCTION 43 KDA HEART PROTEIN) 816 GJA4: (GJA4) GAP JUNCTION ALPHA-4 NM 002060 1.58.45% PROTEIN (CONNEXIN37) (CX37).

818 GJA5: (GJA5) GAP JUNCTIONALPHA-5 NM 181703 PROTEIN (CONNEXIN 40) (CX40). GJA7: (GJA7 ORCXN-45) GAP JUNCTION NM OO5497 O.99.20% ALPHA-7 PROTEIN (CONNEXIN 45) (CX45) 829 GJB5: (GJB5 ORCXN-31.1) GAP JUNCTION NM OO5268 BETA-5 PROTEIN (CONNEXIN 31.1) (CX31.1). 845 EAAT4: (SLC1A6 OR EAAT4) EXCITATORY P48,664 NM 005071 AMINO ACID TRANSPORTER4 (SODIUM DEPENDENT GLUTAMATEFASPARTATE TRANSPORTER). PTHR2: (PTHR2) PARATHYROID NM 005048 HORMONE RECEPTOR PRECURSOR (PTH2 RECEPTOR). PTHR1: (PTHR1 ORPTHR) PARATHYROID Q03431 NM OOO316 1.53.23% HORMONEPARATHYROID HORMONE RELATED PEPTIDE RECEPTOR PRECURSOR (PTH/PTHR RECEPTOR). 191 COL18A1 1: (COL18A1) COLLAGEN ALPHA NM O30582 1.11.7% (XVIII) CHAIN CONTAINS: NM 130445 ENDOSTATIN). FZD3: (FZD3) FRIZZLED 3 PRECURSOR NM O17412 (FRIZZLED-3) (FZ-3) (HFZ3) (MFZ3) (RFZ3). 210 FZD4: (FZD4) WNT RECEPTOR FRIZZLED-4, NM 0121.93 1.34.32% FRIZZLED 4 PRECURSOR (FRIZZLED-4) (FZ 4) (HFZ4) (FZE4) (MFZ4) (RFZ4) (CD344 ANTIGEN). 248 TP53BP1: (TP53BP1) TUMOR SUPPRESSOR NM OO5657 O.85.12% P53-BINDING PROTEIN 1 (P53-BINDING PROTEIN 1) (53BP1).

1259 SFRP2: (SFRP2 ORFKSG12 OR FRP2 OR NM OO3013 SARP1) SECRETED FRIZZLED-RELATED PROTEIN 2 PRECURSOR (SFRP-2) (SECRETED APOPTOSIS-RELATED PROTEIN 1) (SARP-1) (FRIZZLED-RELATED PROTEIN 2) (FRP-2) (PANCREASTUMOR RELATED PROTEIN FKSG12) (UNQ361/PRO697). US 2008/O 159999 A1 Jul. 3, 2008 23

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 282 BMP2: (BMP2 OR BMP2A OR BMP-2) BONE P12643 NM OO1200 1.67.17% MORPHOGENETIC PROTEIN 2 PRECURSOR (BMP-2) (BMP-2A). 284 BMP3: (BMP3 OR BMP-3) BONE P12645 NM 001201. MORPHOGENETIC PROTEIN3 PRECURSOR (BMP-3) (OSTEOGENIN) (BMP-3A). 287 BMP6: (BMP6 OR BMP-6 ORVGR1) BONE P22004 NM OO1718 MORPHOGENETIC PROTEIN 6 PRECURSOR 291 BMP8A-BMP8B HUMAN: (BMP8) BONE NM OO1720 1.12.13% MORPHOGENETIC PROTEIN 8 PRECURSOR NM 181809 (BMP-8) (BMP-8A) (BMP-8B) (OSTEOGENIC PROTEIN 2) (OP 2). 294 CTGF: (CTGF ORHCS24) CONNECTIVE NM OO1901 O.87.15% TISSUE GROWTH FACTOR PRECURSOR (HYPERTROPHIC CHONDROCYTE SPECIFIC PROTEIN 24). GDF1: (GDF1 OR GDF-1) EMBRYONIC NM OO1492 G ROWTHDIFFERENTIATION FACTOR1 C GDF3: (GDF3) GROWTH DIFFERENTIATION NM 020634 A.C TO R 3 G DF 3 OR GDF-3 ORVGR-2) ROWTHDIFFERENTIATION FACTOR 3 RSOR (GDF-3) (VG-1-RELATED 312 : (GDF8 ORMSTN) NM OO5259 1.34.29% ROWTHDIFFERENTIATION FACTOR8 RECURSOR (GDF-8) (MYOSTATIN). 314 F9: (GDF9) GROWTHDIFFERENTIATION O60383 NM OO5260 ACTOR9 PRECURSOR (GDF-9). 316 DNF: (GDNF) GLIAL CELL LINE-DERIVED NM 000514 EUROTROPHICFACTOR PRECURSOR. NM 199231 NM 199234 326 (NHBB: (INHBB) INHIBIN BETA B CHAIN NM 002193 PRECURSOR (ACTIVIN BETA-B CHAIN). 348 PDGFA: (PDGFAORRPA1 ORPDGF1) PDGA NM 002607 PLATELET-DERIVED GROWTH FACTOR, A NM 033023 CHAIN PRECURSOR (PDGF A-CHAIN) (PDGF-1) (PLATELET-DERIVED GROWTH FACTORALPHA POLYPEPTIDE) (PDGF A CHAIN). 1350 PDGFB: (PDGFBOR PDGF2 OR SIS) NM 002608 PLATELET DERIVED GROWTH FACTORB NM 033016 CHAIN PRECURSOR (PDGF B-CHAIN) (PLATELET-DERIVED GROWTH FACTOR BETA POLYPEPTIDE) (PDGF-2) (C-SIS) (BECAPLERMIN). 1430 VEGFB: (VEGFB ORVRF) VASCULAR Q16528 P49765 NM O03377 1.16.35% ENDOTHELLAL GROWTH FACTORB PRECURSOR (VEGF-B) (VEGF RELATED FACTOR). 1436 VEGF: (VEGF ORVEGFA) VASCULAR NM 001025366 ENDOTHELLAL GROWTH FACTOR NM 00102.5367 PRECURSOR (VEGF) (VASCULAR NM 001025368 PERMEABILITY FACTOR) (VPF)(VEGF A) NM 001025369 NM 001025370

1438 VWF: (F8VWF ORVWF) VON NM 000552 WILLEBRAND FACTOR PRECURSOR 1440 CER1: (CER1 ORCER-L) CERBERUS 1 NM 005454 1.49.11% (CERBERUS-LIKE). (CER1 ORCER-1 OR CERR1) CERBERUS 1 (CERBERUS HOMOLOG) CERBERUS-RELATED PROTEIN (CERBERUS-RELATED 1. 1442 WISP3: (WISP3 ORCCN6 OR DJ142L7.3 OR NM OO3880 LIBC) WNT1 INDUCIBLESIGNALING NM 130396 PATHWAY PROTEIN 3 PRECURSOR (WISP NM 198239 3) (CONNECTIVE TISSUE GROWTH FACTOR (NOV, GIG) LIKE PROTEIN US 2008/O 159999 A1 Jul. 3, 2008 24

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (WISP3) (CONNECTIVE TISSUE GROWTH FACTOR RELATED PROTEIN WISP-3) (LOST IN INFLAMMATORY BREAS 1447 SLIT1: (SLIT1 ORKIAA0813 ORMEGF4) NM OO3061 SLIT HOMOLOG 1 PROTEIN PRECURSOR (SLIT-1) (MULTIPLE EPIDERMAL GROWTH FACTOR-LIKE DOMAINS 4). 146S VEGFD: (FIGF ORVEGF-D) VASCULAR O43915 NM 004469 ENDOTHELLAL GROWTH FACTORD (C- FOS INDUCED GROWTH FACTOR). 1485 SYT11: (SYT11 OR KIAAO080) NM 152280 SYNAPTOTAGMIN-11 (SYNAPTOTAGMIN XI) (SYTXI).

1497 PRKCB 1: (PRKCB1 OR PRKCB OR PKCB) NM OO2738 PROTEIN KINASEC, BETA TYPE (EC NM 212535 2.7.1.37) (PKC-BETA) (PKC-B).

1499 PRKCB 2: (PRKCB1 OR PRKCB OR PKCB) NM OO2738 PROTEIN KINASEC, BETA TYPE (EC NM 212535 2.7.1.37) (PKC-BETA) (PKC-B).

1503 PRKCE: (PRKCE OR PKCE) PROTEIN NM OO5400 KINASEC, EPSILON TYPE (EC 2.7.1. ) (NPKC-EPSILON). 1507 PRKCH: (PRKCHOR PKCL) PROTEIN NM OO6255 1.36.26% KINASEC, ETA TYPE (EC 2.7.1.- ) (NPKC ETA) (PKC-L). 1552 SYT1: (SYT1 OR SYT) SYNAPTOTAGMINI P21579 NM OO5639 145.43% (P65). 1623 TIAM: (TIAM) T-LYMPHOMA INVASION Q13009 NM OO3253 AND METASTASIS INDUCING PROTEIN 1 (TIAM1 PROTEIN). 1691 ACTB: (ACTB) BETA1, CYTOPLASMIC NM 001101 O.90.5% (BETA-ACTIN) ACTIN, CYTOPLASMIC 1. 1710 MAPT: (MAPTORMTBT1 ORTAU) NM 005910 MICROTUBULE-ASSOCIATED PROTEIN NM O16834 TAU (NEUROFIBRILLARY TANGLE NM O16835 PROTEIN) (PAIRED HELICAL FILAMENT NM O16841 TAU) (PHF-TAU). 743 APOE: (APOE) APOLIPOPROTEIN E NM 000041 O.23. PRECURSOR (APO-E). 761 SNCA: (SNCA OR NACP) ALPHA SYNUCLEIN (NON-A BETA COMPONENT OF ADAMYLOID) (NACP). 765 SNCG: (SNCG OR BCSG 1) GAMMA 1.30, 6% SYNUCLEIN (PERSYN) (BREAST CANCER SPECIFIC GENE 1 PROTEIN). 811 CYP2C9 HUMAN: (CYP2C9) CYTOCHROME P11713 Q16756 NM 000771 1.53, 196 P450 2C9 (EC 1.14.14.1) (CYPIIC9) (P450 PB Q16872 P11712 1) (P450 MP-4) (S-MEPHENYTOIN 4 HYDROXYLASE) (P-450MP). 915 CSK: (CSK) TYROSINE-PROTEIN KINASE P41240 Q6FGZ6 NM 004383 1.51, 79% CSK (EC 2.7.1.112) (C-SRC KINASE) (PROTEIN-TYROSINE KINASE CYL). 930 PKCD: (PRKCD OR PKCD) PROTEIN Q05655 Q15144 NM OO6254 1.36 59 KINASEC, DELTA TYPE (EC 2.7.1. ) (NPKC NM 212539 DELTA). 953 PIK3CG: (PIK3CG) NM 002649 PHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT, GAMMA ISOFORM (EC 2.7.1.137) (PI3-KINASE P110 SUBUNIT GAMMA) (PTDINS-3-KINASE P110) (PI3K). 2009 CXCR4: (CXCR4 OR LESTRORCMKAR4 OR Q9UKN2 NM OO3467 SDF1R) C-X-C CHEMOKINE RECEPTOR O60835 P61073 TYPE 4 (CXC-R4) (CXCR-4) (SDF-1 P30991 PS6438 US 2008/O 159999 A1 Jul. 3, 2008 25

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 RECEPTOR) (STROMAL CELL-DERIVED FACTOR 1 RECEPTOR) (FUSIN) (LEUKOCYTE-DERIVED SEVEN TRANSMEMBRANE DOMAIN RECEPTOR) (LCR1) (FB22) (NPYRL) (HM89) (CD184 ANT 2031 GAD1 1: (GAD1 OR GAD) GLUTAMATE NM 000817 DECARBOXYLASE, 67 KDA. ISOFORM (EC 4.1.1.15) (GAD-67) (67 KDA GLUTAMIC ACID DECARBOXYLASE). 2035 CALB1: (CALB1 ORCAB27) CALBINDIN P05937 NM 004929 (VITAMIN D-DEPENDENT CALCIUM BINDING PROTEIN, AVIAN-TYPE) (CALBINDIN D28) (D-28K). EAAT1: (SLC1A3 OR EAAT1) EXCITATORY P43003 NM OO4172 AMINO ACID TRANSPORTER1 (SODIUM DEPENDENT GLUTAMATEFASPARTATE TRANSPORTER 1) (GLIAL GLUTAMATE RANSPORTER) (GLAST1) 2043 AAT2 1: (SLC1A2 OR EAAT2 OR GLT1) P43004 Q14417 NM OO4171 TATORY AMINO ACID NSPORTER2 (SODIUM-DEPENDENT TAMATEFASPARTATE TRANSPORTER 2047 RIK1: (GRIK1 OR GLUR5) GLUTAMATE Q86SU9 P39086 NM 000830 ECEPTOR, IONOTROPIC KAINATE 1 Q13001 NM 175611 RSOR (GLUTAMATE RECEPTOR5) (GLUR-5)EUC (EXCITATORY AMINO ACID ECEPTOR3) (EAA3). 2049 RI K2 : (GRIK2 OR GLUR6) GLUTAMATE NM021956 ECEPTOR, IONOTROPIC KAINATE 2 NM 175768 RSOR (GLUTAMATE RECEPTOR6) I U 6) (EXCITATORY AMINO ACID ECEPTOR4) (EAA4). 2053 RIA. : (GRIA1 OR GLUR1 OR GLUH1) NM OOO827 1.17.5% LUTAMATE RECEPTOR 1 PRECURSOR G LUR-1) (GLUR-A) (GLUR-K1) G LUTAMATE RECEPTORIONOTROPIC, MPA 1). 2055 RIA2: (GRLA2 OR GLUR2) GLUTAMATE NM OOO826 RECEPTOR2 PRECURSOR (GLUR-2) (GLUR B) (GLUR-K2) (GLUTAMATE RECEPTOR IONOTROPIC, AMPA 2). 2104 GDF10: (GDF10 OR BMP3B) BONE NM 004962 MORPHOGENETIC PROTEIN3B PRECURSOR (BMP-3B) HADIFFERENTIATION FACTOR GDF-10) (BONE INDUCING PROTEIN) (BIP). 2106 DF5 ORCDMP1) NM 000557 ADIFFERENTIATION FACTORS PRECURSOR (GDF-5) (CARTILAGE DERIVED MORPHOGENETIC PROTEIN 1) (CDMP-1). 2108 INHBA: ( (NHBA) INHIBIN BETA A CHAIN P08476 Q14599 NM 002192 O.38.8% PRECURSOR (ACTIVIN BETA-ACHAIN) (ERYTHROID DIFFERENTIATION PROTEIN) (EDF). 2179 TGFB2: (TGFB2) TRANSFORMING NM 003238 FACTOR BETA. 2 PRECURSOR CA2) (GLIOBLASTOMA-DERIVED UPPRESSOR FACTOR) (G-TSF) ELL GROWTH INHIBITOR) (POLYERGIN) (CETERMIN). 21.83 VEGC: (VEGFC) VASCULARENDOTHELIAL P49767 NM 005429 O.S8.12% GROWTH FACTORC PRECURSOR(VEGF C) (VASCULARENDOTHELLAL GROWTH FACTOR RELATED PROTEIN) (VRP) (FLT4 LIGAND) (FLT4-L). 21.89 PLCB1: (PLCB1) 1 NM O15192 1.40.4% PHOSPHATIDYLINOSITOL-4,5- NM 182734 BISPHOS PHATE PHOSPHODIESTERASE BETA 1 (EC 3.1.4.11) (PLC-BETA-1) (PHOSPH OLIPASEC-BETA-1) (PLC-I) (PLC US 2008/O 159999 A1 Jul. 3, 2008 26

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 54). KIAA0581 PROTEIN DKFZP434AO814

21.93 PLCG1: (PLCG1 OR PLC1) 1 NM 002660 1.22—% PHOSPHATIDYLINOSITOL-4,5- NM 182811 BISPHOSPHATE PHOSPHODIESTERASE GAMMA 1 (EC 3.14.11) (PLC-GAMMA-1) OLIPASEC-GAMMA-1) (PLC-II) (PLC-148). 2195 : (PLCG2) 1 NM 002661 PHOSPHATIDYLINOSITOL-4,5- BISPHOSPHATE PHOSPHODIESTERASE GAMMA 2 (EC 3.14.11) (PLC-GAMMA-2) (PHOSPHOLIPASEC-GAMMA-2) (PLC-IV). 21.96 PLCD1: (PLCD1) 1 P511.78 NM OO6225 PHOSPHATIDYLINOSITOL-4,5- BISPHOSPHATE PHOSPHODIESTERASE DELTA 1 (EC 3.1.4.11) (PLC-DELTA-1) (PHOSPHOLIPASE C-DELTA-1) (PLC-III). CYP3A7 HUMAN: (CYP3A7) P24.462 NM 000765 CYTOCHROME P450 3A7 (EC 1.14.14.1) (CYPIIIA7) (P450-HFLA). 2211 GAPDH: (GAPDH OR GAPD) NM 002046 GLYCERALDEHYDE-3-PHOSPHATE D ROGENASE (EC 1.2.1.12) (GAPDH). 2223 PLP1: (PLP1 OR PLP) MYELIN NM 000533 1.61.18% PROTEOLIPID PROTEIN (PLP) NM 199478 (LIPOPHILIN) (CONTAINS: MYELIN PROTEIN DM-20). 2260 COL1A1: (COL1A1) COLLAGENALPHA 1 (I) P78441 Q13896 NM OOOO88 O.31.11% CHAIN PRECURSOR. Q13902 Q13903 Q14992 Q15201 Q16050 Q7KZ30 Q7KZ34 Q 2262 COL10A1: (COL10A1) COLLAGEN ALPHA Q03692 NM 000493 1(X) CHAIN PRECURSOR. 2264 COL11A1: (COL11A1) COLLAGEN ALPHA NM OO1854 1(XI) CHAIN PRECURSOR. NM 080629 NM 080630 2266 COL12A1: (COL12A1) COLLAGEN ALPHA NM 004370 1(XII) CHAIN PRECURSOR. NM 080645 2271 COL14A1: (COL14A1 ORUND) COLLAGEN NM 021110 ALPHA1(XIV) CHAIN PRECURSOR (UNDULIN). 2275 COL15A1: (COL15A1) COLLAGEN ALPHA NM OO1855 1(XV) CHAIN PRECURSOR. 2277 COL16A1: (COL16A1) COLLAGEN ALPHA NM OO1856 O.32.12% 1(XVI) CHAIN PRECURSOR. 2281 COL18A1 2: (COL18A1) COLLAGEN ALPHA NM O30582 1(XVIII) CHAIN CONTAINS: NM 130445 ENDOSTATIN). 2285 COL2A1: (COL2A1) COLLAGENALPHA 1 (II) NM 001844 CHAIN PRECURSOR CONTAINS: NM 03.3150 CHONDROCALCIN) (T1) COLLAGEN ALPHA1 TYPE II (T1 MRNA).

2289 COL4A1: (COL4A1) COLLAGENALPHA NM OO1845 O42.5% 1(IV) CHAIN PRECURSOR (ARRESTEN). 2293 COL6A1: (COL6A1) COLLAGEN (VI) NM 001848 1.10.9% ALPHA-1 CHAIN (FRAGMENT) COLLAGEN ALPHA 1 (VI) CHAIN PRECURSOR. 2295 COL7A1: (COL7A1) COLLAGENALPHA NM OOOO94 O.17.9% 1(VII) CHAIN PRECURSOR (LONG-CHAIN COLLAGEN) (LC COLLAGEN). 2297 COL8A1: (COL8A1) COLLAGENALPHA P27658 Q96D07 NM OO1850 0.82.14% 1(VIII) CHAIN PRECURSOR (ENDOTHELIAL NM 020351 COLLAGEN). US 2008/O 159999 A1 Jul. 3, 2008

TABLE 4-continued Array # Geneti Name RefSeq, 4800038 2299 COL9A1 1: (COL9A1) COLLAGEN ALPHA NM OO1851 1(IX) CHAIN PRECURSOR. NM O78485 Q9H152 Q99225 Q13699 Q13700 P20849 QSTF52 Q 2301 COL1A2: (COL1A2). COLLAGENALPHA2(I) Q9UEB6 NM OOOO89 0.40.10% CHAIN PRECURSOR. Q9UPHO PO8123 PO2464 Q13897 Q13997 Q13998 Q14038 Q14057 Q 2303 COL11A2: (COL11A2) COLLAGEN ALPHA Q99866 Q9UIP9 NM 080679 1.27.61% 2(XI) CHAIN PRECURSOR. P13942 Q13273 NM 080680 Q13271 Q13272 NM 080681 Q07751 2307 COL5A2: (COL5A2) COLLAGENALPHA2(V) P05997 NM OOO393 CHAIN PRECURSOR. 2309 COL6A2 1: (COL6A2) COLLAGEN ALPHA P12110 Q14049 NM 001849 1.43.2% 2(VI) CHAIN PRECURSOR Q9UML3 (DKFZP586E1322). Q13909 Q13910 Q13911 Q16259 Q16597 2313 COL9A2: (COL9A2) COLLAGEN TYPE IX Q14055 NM OO1852 ALPHA 2 CHAIN (ALPHA-2 IX COLLAGEN). 2315 COL4A3: (COL4A3) COLLAGENALPHA NM 000091 1.11.23% 3(IV) CHAIN PRECURSOR 2319 COL9A3: (COL9A3) ALPHA-3 TYPE IX NM OO1853 1.24.27% COLLAGEN. 2321 COL4A4: (COL4A4) COLLAGENALPHA NM 000092 1.59.61% 4(IV) CHAIN PRECURSOR. 2324 TGA7: (ITGA7) INTEGRIN ALPHA-7 NM OO2206 1.16 —% (INTEGRIN ALPHA 7 CHAIN) (INTEGRIN ALPHA-7) (INTEGRINA7). 2326 TGA8: (ITGA8) INTEGRINE ALPHA-8 NM 003638 1.39.18% (INTEGRINA8). 2328 TGA9: (ITGA9) INTEGRTN ALPHA-9 NM OO2207 1.18.13% PRECURSOR(INTEGRIN ALPHA-RLC) (INTEGRINA9). 2330 TGB5: (ITGB5) INTEGRIN BETA-5 P18084 NM OO2213 O.96.9% PRECURSOR(INTEGRINB5). 2332 TGB6: (ITGB6) INTEGRIN BETA-6 P18564 Q16500 NM OOO888 PRECURSOR(INTEGRINB6). QOVA95 Q53RG5 Q53RR6 2334 TGB7: (ITGB7). INTEGRIN BETA-7 P26010 NM OOO889 PRECURSOR(INTEGRINB7). 2336 TGB8: (ITGB8) INTEGRIN BETA-8 NM 002214 URSOR 2338 (SERPINE1 OR PAI1 OR PLANH1) P05121 NM OOO602 O.13.7% SMINOGENACTIVATORINEHIBITOR-1 RSOR (PAI-1) (ENDOTHELIAL INOGEN ACTIVATOR INHIBITOR) ). 2340 SERPINB2: (SERPINB2 OR PAI2 OR NM OO2575 PLANH2) PLASMINOGENACTIVATOR BITOR-2. PRECURSOR(PAI-2) (PLACENTAL PLASMINOGEN ACTIVATOR (NHIBITOR) (MONOCYTE ARG-SERPIN) (UROKINASE INHIBITOR). 2342 ADAM17: (ADAM17 ORTACE ORCSVP) O60226 P78536 NM OO31.83 ADAM 17 PRECURSOR (EC 3.4.24- ) (A NM O21832 DISINTEGRIN AND METALLOPROTEINASE DOMAIN 17) (TNF-ALPHACONVERTING ENZYME) (TNF-ALPHACONVERTASE) (SNAKE VENOM-LIKE PROTEASE) (CD156B ANTIGEN). 2344 TIMP1: (TIMP1 OR TIMP OR CLGI) NM OO3254 O.76.13% METALLOPROTEINASE INHIBITOR1 PRECURSOR (TIMP-1) (ERYTHROID POTENTIATING ACTIVITY) (EPA) (TISSUE US 2008/O 159999 A1 Jul. 3, 2008 28

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (NHIBITOR OF METALLOPROTEINASES) (FIBROBLAST COLLAGENASE INHIBITOR) (COLLAGENASE INHIBITOR). 2346 TIMP2: (TIMP2) METALLOPROTEINASE Q9UDF7 NM OO3255 O.89.1% (NHIBITOR2 PRECURSOR (TIMP-2) P16035 Q93006 (TISSUE INHIBITOR OF Q16121 METALLOPROTEINASES-2) (CSC-21K). 2348 TIMP3: (TIMP3) METALLOPROTEINASE NM OOO362 O.31.6% (NHIBITOR3 PRECURSOR (TIMP-3) (TISSUE INHIBITOR OF METALLOPROTEINASES-3) (MIG-5 PROTEIN). 2352 PLAT: (PLAT) TISSUE-TYPE NM OOO930 O.28.11% PLASMINOGENACTIVATOR PRECURSOR NM OOO931 (EC 3.4.21.68) (TPA) (T-PA) (T- NM 033011 PLASMINOGEN ACTIVATOR) (ALTEPLASE) (RETEPLASE) CONTAINS: TISSUE-TYPE PLASMINOGEN ACTIVATORCHAINA; TISSUE-TYPE PLASMINOGENACTIVATOR CHAIN B). UPA: (PLAU) UROKINASE-TYPE Q15844 Q16618 NM 002658 1.31f4% PLASMINOGENACTIVATOR PRECURSOR POO749 (EC 3.4.21.73) (UPA) (U-PLASMINOGEN Q969W6 ACTIVATOR). 2356 BMP7: (BMP7 OR BMP-7 OR OP1) BONE NM OO1719 MORPHOGENETIC PROTEIN 7 PRECURSOR (BMP-7) (OSTEOGENIC PROTEIN 1) (OP-1). 2360 LAMA 1: (LAMA1 ORLAMA) LAMININ P25391 NM OO5559 ALPHA-1 CHAIN PRECURSOR (LAMININ A CHAIN). 2362 LAMA2: (LAMA2 OR LAMM) LAMININ NM 000426 ALPHA-2 CHAIN PRECURSOR (LAMININ M CHAIN) (MEROSIN HEAVY CHAIN). 2364 LAMA3: (LAMA3) LAMININ ALPHA-3 NM 000227 0.60-% CHAIN PRECURSOR (EPILIGRIN 170 KDA NM 198129 SUBUNIT) (E170). 2366 LAMA4: (LAMA4) LAMININ ALPHA-4 NM 002290 CHAIN PRECURSOR.

2368 LAMA5: (KIAAO533 ORLAMA5) KIAAO533 NM OO5560 1.18.36% PROTEIN (LAMININ ALPHA5 CHAIN) (FRAGMENT). 2370 LAMB1: (LAMB1) LAMININ BETA-1 CHAIN NM 002291 0.75.3% PRECURSOR (LAMININ B1 CHAIN). 2375 LAMB3: (LAMB3) LAMININ BETA-3 CHAIN O NM 000228 O.36.15% PRECURSOR (LAMININ B1K CHAIN) Q (KALININ B1 CHAIN). Q9UJL1 Q13751 Q14733 2377 LAMG1: (LAMC1 ORLAMB2) LAMININ 11047 NM 002293 1.01.11% GAMMA-1 CHAIN PRECURSOR(LAMININ B2 CHAIN). 2385 EPIPHYCAN: (DSPG3) SMALL Q99645 Q8NETS NM OO4950 CHONDROITINDERMATAN SULFATE PROTEOGLYCAN PRECURSOR (PG-LB) (PGLB) (EPIPHYCAN) (DERMATAN SULFATE PROTEOGLYCAN 3) (DSPG3). COL4A6: (COL4A6) COLLAGEN TYPE IV A6 NM OO1847 CHAIN. NM 033641

2403 COL4A5: (COL4A5) COLLAGENALPHA NM 000495 5(IV) CHAIN PRECURSOR. NM 033380 NM 03.3381 2423 AGC1: (AGC1 ORCSPG1 ORAGC) NM 001135 AGGRECAN CORE PROTEIN PRECURSOR NM 013227 (CARTILAGE-SPECIFIC PROTEOGLYCAN US 2008/O 159999 A1 Jul. 3, 2008 29

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 CORE PROTEIN) (CSPCP) (CHONDROITIN SULFATE PROTEOGLYCAN CORE PROTEIN 1) (AGGRECAN1). 2425 AGRIN: (AGRN) AGRIN PRECURSOR. NM 198576 O45.13%

2429 BAMACAN: (BAMORSMCD ORHCAP OR NM OO5445 1.51.5% CSPG6 OR SMC3 OR SMC3L1 OR BMH) STRUCTURAL MAINTENANCE OF CHROMOSOME 3 (CHONDROITIN SULFATE PROTEOGLYCAN 6) (CHROMOSOME SEGREGATION PROTEIN SMCD) (BAMACAN) BASEMENT MEMBRANE-ASSOCIATED CHONDROITIN PROTEOGLYCAN) (HCAP). 2433 BMP1 1: (BMP1 OR PCP-3) BONE NM OO6129 0.4914% MORPHOGENETIC PROTEIN 1 PRECURSOR (EC 3.4.24- ) (BMP-1) PROCOLLAGEN C PROTEINASE 3. 2435 BMP5: (BMP5) BONE MORPHOGENETIC NM 021073 PROTEINS PRECURSOR(BMP-5). 2439 BCAN: (BCAN) BREVICAN CORE PROTEIN NM 021948 PRECURSOR (CHONDROITIN SULFATE NM 198427 PROTEOGLYCAN BEHAB/BREVICAN).

BROMODULIN: (FMOD OR FM) NM 002023 1.30.8% FIBROMODULIN PRECURSOR (FM) (COLLAGEN-BINDING 59 KDA PROTEIN). 2453 FN1: (FN1 ORFN) FIBRONECTIN NM 002026 O.25.2% PRECURSOR (FN) (COLD-INSOLUBLE NM 212474 GLOBULIN) (CIG). NM 212475 NM 212476 NM 212478 NM 212482 2459 IBSP: (IBSP OR BNSP) BONE NM OO4967 SIALOPROTEIN II PRECURSOR (BSP II) (CELL-BINDING SIALOPROTEIN) (INTEGRIN-BINDINGSIALOPROTEIN). 2473 LUMICAN: (LDC) LUMICAN PRECURSOR NM 002345 1.66.17% (LUM) (KERATAN SULFATE PROTEOGLYCAN). 2487 MMP10: (MMP10 OR STMY2) PO9238 NM OO2425 STROMELYSIN-2 PRECURSOR (EC 3.4.24.22) (MATRIX METALLOPROTEINASE-10) (MMP-10) (TRANSIN-2) (SL-2). 2489 MMP11: (MMP11 OR STMY3) NM OO5940 0.78, -96 STROMELYSIN-3 PRECURSOR (EC 3.4.24- ) (MATRIX METALLOPROTEINASE-11) (MMP-11) (ST3) (SL-3). 2491 MMP12: (MMP12 OR HME) MACROPHAGE P39900 NM 002.426 1.37.1796 METALLOELASTASE PRECURSOR (EC 3.4.24.65) (HME) (MATRIX METALLOPROTEINASE-12) (MMP-12). 2493 MMP13: (MMP13) COLLAGENASE3 P454.52 NM OO2427 PRECURSOR (EC 3.4.24- ) (MATRIX METALLOPROTEINASE-13) (MMP-13). 2495 MMP14: (MMP14 ORMMP-X1) MATRIX Q92678 P50281 NM OO4995 1.126% METALLOPROTEINASE-14 PRECURSOR (EC 3.4.24- ) (MMP-14) (MEMBRANE-TYPE MATRIX METALLOPROTEINASE 1) (MT MMP 1) (MTMMP1). 2497 MMP15: (MMP15) MATRIX Q14111 P51511 NM 002428 O.82.13% METALLOPROTEINASE-1S PRECURSOR (EC 3.4.24- ) (MMP-15) (MEMBRANE-TYPE MATRIX METALLOPROTEINASE 2) (MT MMP 2) (MTMMP2). US 2008/O 159999 A1 Jul. 3, 2008 30

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 2499 MMP16 1: (MMP16 ORMMPX2) MATRIX Q14824 P51512 NM OO5941 METALLOPROTEINASE-16 PRECURSOR Q52H48 (EC 3.4.24- ) (MMP-16) (MEMBRANE-TYPE MATRIX METALLOPROTEINASE 3) (MT MMP3) (MTMMP3) (MMP-X2). MMP2: (MMP2 OR CLG4A) 72 KDA TYPE IV PO8253 NM 004530 O.94.5% COLLAGENASE PRECURSOR (EC 3.4.24.24) (72 KDAGELATINASE) (MATRIX METALLOPROTEINASE-2) (MMP-2) (GELATINASEA) (TBE-1) 2503 MMP3: (MMP3 OR STMY1) STROMELYSIN NM 002422 1 PRECURSOR (EC 3.4.24.17) (MATRIX METALLOPROTEINASE-3) (MMP-3) (TRANSIN-1) (SL-1). 2505 MMP7: (MMP7 ORMPSL1 OR PUMP1) NM OO2423 MATRILYSIN PRECURSOR (EC 3.4.24.23) (PUMP-1 PROTEASE) (UTERINE METALLOPROTEINASE) (MATRIX METALLOPROTEINASE-7) (MMP-7) (MATRIN). 2509 MMP9: (MMP9 OR CLG4B) 92 KDA TYPE IV NM 004994 COLLAGENASE PRECURSOR (EC 3.4.24.35) (92 KDAGELATINASE) (MATRIX METALLOPROTEINASE-9) (MMP-9) (GELATINASEB) (GELB). L1CAM: (L1CAMORCAML1 OR MIC5) P32004 Q8TA87 NM 000425 NEURAL CELLADHESIONMOLECULE L1 NM 024003 PRECURSOR (N-CAM L1) (CD171 ANTIGEN). 2513 NEUROCAN: (CSPG3 OR NEUR) NMOO4386 1.17.16% NEUROCAN (PGCN HUMAN). 2515 NIDOGEN: (NID) NIDOGEN PRECURSOR NM OO2508 (ENTACTIN).

2517 SPP1: (SPP1 OR OPN) OSTEOPONTIN NM OOO582 PRECURSOR (BONESIALOPROTEIN 1) NM OO1040.058 (URINARY STONE PROTEIN) (SECRETED NM OO1040.060 PHOSPHOPROTEIN 1) (SPP-1) (NEPHROPONTIN) (UROPONTIN). 2519 OSF: (OSTF1 OR SH3D3 OR SH3P2) NM 012383 1.28.34% OSTEOCLAST STIMULATING FACTOR1 (SH3 DOMAIN PROTEIN3). 2521 BGLAP: ((BGLAP1 AND BGLAP2) AND PO2818 NM 1991.73 0.98.44% (BGLAP-RS1)) OSTEOCALCIN PRECURSOR (GAMMA-CARBOXYGLUTAMIC ACID CONTAINING PROTEIN) (BONE GLA PROTEIN) (BGP) (OSTEOCALCIN RELATED PROTEIN PRECURSOR(OC-X) (NEPHROCALCIN). 2527 DCN: (DCN) BONE PROTEOGLYCAN II NM OO1920 PRECURSOR (PG-S2) (DECORIN) (PG40) NM 133503 (PGS2) NM 133504 NM 133505 2531 SDC4: (SDC4) SYNDECAN-4 PRECURSOR NM OO2999 (AMPHIGLYCAN) (SYND4) (RYUDOCAN CORE PROTEIN). 2541 TNC: (TNC OR HXB) TENASCIN P24821 Q15567 NM 002160 O.61.17% PRECURSOR (TN) (HEXABRACHION) Q14583 (CYTOTACTIN) (NEURONECTIN) (GMEM) (JI) (MIOTENDINOUSANTIGEN) (GLIOMA ASSOCIATED-EXTRACELLULARMATRIX ANTIGEN) (GP 150-225) (TENASCIN-C) (TN C). 2545 TENASCINX: (TNXB ORTNXORXB OR NM 019105 HXBL) TENASCIN-X PRECURSOR (TN-X) NM O32470 (HEXABRACHION-LIKE) (TNXB ISOFORM 1) (TNXA). 2549 THBS2: (THBS2 ORTSP2) NM OO3247 O.90.1% THROMBOSPONDIN 2 PRECURSOR (THROMBOSPONDIN2). US 2008/O 159999 A1 Jul. 3, 2008 31

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 2555 THBS1: (THBS1 ORTSP1 ORTSP) PO7996 Q15667 NM OO3246 THROMBOSPONDIN 1 PRECURSOR (THROMBOSPONDIN1). 2557 COMP: (COMP) CARTILAGE OLIGOMERIC Q8N4T2 NM OOOO95 MATRIX PROTEIN PRECURSOR (COMP) Q16389 P49747 (THROMBOSPONDIN5). Q16388 O14592 2560 MMP19: (MMP19 ORMMP18 OR RASI) O15278 O95606 NM OO1032360 O.80.12% MATRIX METALLOPROTEINASE-19 Q99580 Q995.42 NM 002429 PRECURSOR (EC 3.4.24- ) (MMP-19) (MATRIX METALLOPROTEINASE RASI) (MMP-18). 2936 IL6: (IL6 ORIFNB2 OR IL-6) INTERLEUKIN NM OOO600 O.04.19% 6 PRECURSOR(IL-6) (B-CELL STIMULATORY FACTOR2) (BSF-2) (INTERFERON BETA-2) (HYBRIDOMA GROWTH FACTOR). 296S BMP4: (BMP4 OR BMP2B ORDVR4 OR NM 001202 BMP-4. ORDVR-4) BONE MORPHOGENETIC NM 130850 PROTEIN 4 PRECURSOR(BMP-4) (BMP-2B). NM 130851 3.018 HPRT: (HPRT1 OR HPRT) HYPOXANTHINE POO492 NM OOO194 GUANINE PHOSPHORIBOSYLTRANSFERASE (EC 2.4.2.8) (HGPRT) (HGPRTASE). 3058 GREM2: (GREM2 OR CKTSF1B2 ORDAND3 NM O22469 OR PRDC) GREMLIN-2 PRECURSOR (CYSTEINE KNOTSUPERFAMILY 1, BMP ANTAGONIST 2) (PROTEIN RELATED TO DAN AND CERBERUS) (FLT21195). 3385 CSPG2 1: (CSPG2) VERSICAN CORE NM 004385 O.24.7% PROTEIN PRECURSOR(LARGE FIBROBLAST PROTEOGLYCAN) (CHONDROITIN SULFATE PROTEOGLYCAN CORE PROTEIN 2) (GLIAL HYALURONATE-BINDING PROTEIN) (GHAP). 3.454 ITGAM: (ITGAMORCR3A ORCD11B) P11215 NM 000632 INTEGRIN ALPHA-M PRECURSOR (CELL SURFACE GLYCOPROTEINMAC-1 ALPHA SUBUNIT) (CR-3 ALPHACHAIN) (CD11B) (LEUKOCYTE ADHESION RECEPTORMO1) (INTEGRIN ALPHA-M) (NEUTROPHIL ADHERENCE RECEPTOR). 3535 JUN: (JUN) TRANSCRIPTION FACTORAP-1 NM OO2228 O.76.38% (ACTIVATOR PROTEIN 1) (AP1) (PROTO ONCOGENE C-JUN) (V-JUNAVIAN SARCOMAVIRUS 17 ONCOGENE HOMOLOG) (P39). ATF2: (ATF2 OR CREB2 OR CREBP1) Q13000 P15336 NM OO1880 CYCLIC-AMP-DEPENDENT TRANSCRIPTION FACTORATF-2 (ACTIVATING TRANSCRIPTION FACTOR2) (CAMP RESPONSEELEMENT BINDING PROTEINCRE-BP1) (HB16). 3562 ATF4: (ATF4) CYCLIC-AMP-DEPENDENT NM OO1675 1.11.3% TRANSCRIPTION FACTORATF-4 (DNA NM 1828.10 BINDING PROTEINTAXREB67) (CYCLIC AMP RESPONSEELEMENT BINDING C ROTEIN 2) (CREB2). 3591 H SPA4 1: (HSPA4 OR HSP110 ORIRP94) P34932 O95756 NM 002154 1.13.10% H EAT SHOCK 70 KDA PROTEIN 4 (HEAT SHOCK 70-RELATED PROTEIN APG-2) (HSP7ORY) (ISCHEMIA RESPONSIVE 94 KDA PROTEIN). 3594 HSPA9: (HSPA9B OR HSPA9 OR GRP75) NM 004134 O.83.6% MITOCHONDRIAL STRESS-7O PROTEIN PRECURSOR (75 KDA GLUCOSE REGULATED PROTEIN) (GRP 75) (PEPTIDE BINDING PROTEIN 74) (PBP74) (MORTALIN) (MOT). 3600 HYOU1: (HYOU1 OR ORP150) 150 KDA NM OO6389 O.63.10% OXYGENREGULATED HSP70 FAMILY PROTEIN (ORP150) (CAB140 OR GRP170) (HYPOXIAUP-REGULATED 1). US 2008/O 159999 A1 Jul. 3, 2008 32

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 3608 EBPB: (CEBPB OR TCF5) NM 005.194 O.96.12% CAATENHANCERBINDING PROTEIN BETA (C/EBP BETA) (NUCLEAR FACTOR NF-IL6) (TRANSCRIPTION FACTOR5). 3614 CEBPG: (CEBPG) CCAAT/ENHANCER NM OO1806 0.725% BINDING PROTEIN GAMMA (C/EBP AMMA). 3622 CREBL1: (CREBL1 ORG13) CYCLIC AMP NM 004381 O.99.19% DEPENDENT TRANSCRIPTION FACTOR ATF-6 BETA (ACTIVATING RANSCRIPTION FACTOR 6B ETA) (ATF6 ETA) (CAMP-RESPONSIVE ELEMENT. NDING PROTEIN-LIKE 1) (CAMP ESPONSEELEMENT BINDING PROTEIN ELATED PROTEIN) (CREB-RP) (G13 ROTE 3644 JUNB: (JUNB) TRANSCRIPTION FACTOR P17275 NM OO2229 1.11.10% JUN B (GOS3). Q96GH3 3676 FOXG1A-FOXG1B: (FOXG1B ORFKHL1) P55315 P55316 NM OO5249 FORKHEAD PROTEING1B (FORKHEAD RELATED PROTEIN FKHL1) (TRANSCRIPTION FACTORBF-1) (BRAIN FACTOR 1) (B F1) (HFK1) (FOXG1 AOR FKHL2) FORKHEAD BOX PROTEING1A (FORKHEAD-RELATED PROTEIN FKHL2) (TRANSCRIPTCION FACTORBF-2). 368O FAST1: (FOXH1 ORFAST1) FORKHEAD O75593 NM OO3923 BOX PROTEIN H1 (FORKHEAD ACTIVIN SIGNAL TRANSDUCER 1) (FAST-1). (FOXH1 OR FAST2) FORKHEAD ACTIVIN SIGNAL TRANSDUCER2. TGF-BETAACTIVIN SIGNAL TRANSDUCERFAST-1P 3684 OR HFH11 OR NM O21953 WINORMPP2) FORKHEAD PROTEIN M1 NM 202002 (FORKHEAD-RELATED PROTEIN FKHL16) NM 202003 (HEPATOCYTE NUCLEAR FACTOR3 FORKHEAD HOMOLOG 11) (HNF-3/FORK HOMOLOG-3) (HFH-11) (WINGED LIX FACTOR FROM INS-1 CELLS) (M- A. S E PHOSPHOPROTEIN 2 3686 : (FOXO1 AORFKHR) FORKHEAD NM OO2015 NO1A(FORKHEAD IN R HA. B DOMYOSARCOMA). 3707 F3A: (FOXA1 OR HNF3A OR TCF3A) NM 004496 PATOCYTE NUCLEAR FACTOR 3 ALPHA (HNF-3A). 3709 HNF3B: (FOXA2 OR HNF3B OR TCF3B) NM O21784 HEPATOCYTE NUCLEAR FACTOR3-BETA NM 153675 (HNF-3B) 3711 NM OO4497 F3G) HEPATOCYTE NUCLEAR FACTOR GAMMA (HNF-3G) (FORK H EAD LATED PROTEIN FKH H3). 3719 XC2: (FOXC2 ORFKHL14 O RMFH1) Q99958 NM OO5251 RKHEAD BOX PROTEIN C2 (FORKHEAD LATED PROTEIN FKHL14) (MESENCHYME FORK HEAD PROTEIN 1) (MFH-1 PROTEIN) (TRANSCRI PTION FACTORFKH-14) 3896 CNP. (CNP) 2',3'-CYCLICNUCLEOTIDE 3'- P09543 NM 033133 1.05.31% PHOSPHODIESTERASE (EC 3. 4.37) (CNP) (CNPASE) (CNPI) (CNPII). 3919 MAP2: (MAP2 ORMTAP2) MICROTUBULE P11137 Q99976 NM OO1039538 ASSOCIATED PROTEIN 2 (MA P2) (MAP-2). Q99975 NM 002374 NM 031845 NM 031847 3929 RPSA: (RPSA ORLAMR1 ORLAMBROR PO8865 P11085 NM 002295 1.31.5% P40-8) 40S RIBOSOMAL PROT EINSA (P40) P12030 Q16471 (34/67 KDA LAMININ RECEPTOR) (COLON Q6IPD1 CARCINOMA LAMININ-BIND ING PROTEIN) (NEM/1CHD4) (MULTIDRUG RESISTANCE ASSOCIATED PROTEINMGR1-AG) (MUSLAMR). US 2008/O 159999 A1 Jul. 3, 2008

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 3945 OSP: (OTMOROSP OR CLDN11) CLAUDIN QSUOP3 O.25.22% 11 (OLIGODENDROCYTE SPECIFIC O75508 PROTEIN) (OLIGODENDROCYTE TRANSMEMBRANE PROTEIN). 3953 S10OB: (S100B) S-100 PROTEIN, BETA PO4271 NM OO6272 CHAIN. 3963 SNAP25A: (SNAP25 OR SNAP) P6088O NM OO3O81 SYNAPTOSOMAL-ASSOCIATED PROTEIN NM 130811 25 (SNAP-25) (SUPER PROTEIN) (SUP). 4042 IKKA: (IKKALPHA ORCHUK) INHIBITOR Q13132 Q92467 NM OO1278 1.05.19% OF NUCLEAR FACTOR KAPPA-B KINASE O14666 O15111 ALPHA SUBUNIT (EC 2.7.1.- )(I KAPPA-B KINASE ALPHA) (IKBKA) (IKK-ALPHA) (IKK-A) (IKAPPAB KINASE) (I-KAPPA-B KINASE 1) (IKK1) (CONSERVED HELIX LOOP-HELIX UBIQUITOUS KINASE) (NUCLEAR FACTO 4045 IKKB: (IKKBORIKBKB) INHIBITOR OF O14920 O7S327 NM OO1556 O.77.16% NUCLEAR FACTORKAPPA B KINASE BETA SUBUNIT (EC 2.7.1. ) (I-KAPPA-B- KINASE BETA) (IKBKB) (IKK-BETA) (IKK B) (I-KAPPA-B KINASE 2) (IKK2) (NUCLEAR FACTORNF-KAPPA-B INHIBITORKINASE BETA) (NFKBIKB). 4064 NFATCB 1: (NFATC1 OR NFATC OR Q15793 O95644 NM OO6162 1.01 % NFAT2) NUCLEAR FACTOR OF Q12865 NM 172387 ACTIVATED T-CELLS, CYTOPLASMIC 1 NM 172389 (NFAT TRANSCRIPTION COMPLEX NM 1723.90 CYTOSOLIC COMPONENT) (NF-ATC1) (NF ATC). NFKB1: (NFKB1) NUCLEAR FACTOR NF NM OO3998 KAPPA-B P105 SUBUNIT (DNA-BINDING FACTOR KBF1) (EBP-1) CONTAINS: NUCLEAR FACTORNF-KAPPA-B PSO SUBUNIT). 4070 NFKB2: (NFKB2) NUCLEAR FACTOR NF O.35.6% KAPPA-B P100 SUBUNIT (H2TF1) (ONCOGENELYT-10) (LYT10) (CONTAINS: NUCLEAR FACTORNF-KAPPA-B PS2 SUBUNIT). NFKB3: (RELA OR NFKB3) NM O21975 O.90.10% TRANSCRIPTION FACTORP65 (NUCLEAR FACTOR NF-KAPPA-B P65 SUBUNIT). 4181 ASCL1: (ASCL1 ORASH1 OR MASH1 OR NM 004316 MASH-1) ACHAETE-SCUTE HOMOLOG 1 (MASH-1) (HASH1). 418S ATH1: (ATOH1 ORATH1) ATONAL Q92858 NM OO5172 PROTEIN HOMOLOG 1 (HELIX-LOOP HELIX PROTEIN HATH-1). 41.97 HIF1A: (HIF1A) HYPOXIA-INDUCIBLE NM OO1530 O.71.8% FACTOR 1 ALPHA (HIF-1 ALPHA) (ARNT NM 181054 INTERACTING PROTEIN) (MEMBER OF PAS PROTEIN 1) (MOP1) (HIF1ALPHA). 41.99 ID1: (ID1 ORID) DNA-BINDING PROTEIN NM 002165 INHIBITORID-1 (ID) NM 181353

ID2: (ID2) DNA-BINDING PROTEIN NM 002166 INHIBITORID-2. ID3: (ID3 OR 1R21 OR HEIR-1) DNA Q02535 O75641 NM 002167 1.33.18% BINDING PROTEIN INHIBITORID-3 (ID LIKE PROTEIN INHIBITOR HLH 1R21) (HELIX-LOOP-HELIX PROTEIN HEIR-1). 4233 NEUROD1: (NEUROD1 OR NEUROD) Q13562 Q13340 NM OO2500 NEUROGENICDIFFERENTIATION FACTOR Q994.55 O00343 1. Q96THO QSU095 Q9UEC8 4237 NEUROG1: (NEUROG1 ORNGN1 ORNGN Q96HE1 NM OO6161 ORNEUROD3 ORATH4C) NEUROGENIN 1 Q92886 US 2008/O 159999 A1 Jul. 3, 2008 34

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (NEUROGENIC DIFFERENTIATION FACTOR3) (NEUROD3) (NEUROGENIC BASIC-HELIX-LOOP-HELIX PROTEIN). 4241 NMYC: (MYCN OR NMYC) N-MYC PROTO NM OO5378 ONCOGENE PROTEIN. TAL1: (TAL1 ORSCLORTCL5) T-CELL NM OO3189 ACUTELYMPHOCYTICLEUKEMIA-1 PROTEIN (TAL-1 PROTEIN) (STEM CELL PROTEIN) (T-CELL LEUKEMIA/LYMPHOMA-5 PROTEIN). 4255 TCF3: (TCF3 ORE2A OR ITF1 OR TCFE2A Q9UPI9 Q14635 NM OO3200 O.87.17% OR ALF2 OR ME2) TRANSCRIPTION Q14636 Q14208 FACTORE2-ALPHA (IMMUNOGLOBULIN P15923 P15883 ENHANCERBINDING FACTOR E12/E47) (TRANSCRIPTION FACTOR-3) (TCF-3) (IMMUNOGLOBULIN TRANSCRIPTION FACTOR-1) (TRANSCRIPTION FACTOR ITF ) (TRANSCRIPTIONAL REGU 4257 TCF4: (TCF4 OR ITF2 OR SEF2) P15884 Q15439 NM OO3199 TRANSCRIPTION FACTOR 4 Q15440 (IMMUNOGLOBULIN TRANSCRIPTION FACTOR2) (RITF-2) (ITF-2) (SL3-3 ENHANCER FACTOR2) (SEF-2) (CLASSA HELIX-LOOP-HELIXTRANSCRIPTION FACTOR ME2). 4275 EBCTF: (EBF) EARLY B-CELL NM 024007 TRANSCRIPTION FACTOR (FRAGMENT). (COE1 OR OLF1) TRANSCRIPTION FACTOR COE1 (OE-1) (O/E-1) (OLFACTORY NEURONAL TRANSCRIPTION FACTOR) -1). 4279 D1: (HAND1 OREHAND) HEARTAND O96004 NM 004.821 RAL CREST DERIVATIVES RESSED PROTEIN TRAEMBRYONICTISSUES, HEART, TONOMICNERVOUS SYTEMAND RAL CREST DERIVATIVES PRESSED PROTEIN 1) (EHAND) (BASIC LIX-LOOP-HELIX PROTEIN HAND1) fE.H ING1). 4289 ES R1: (HESR-1 ORCHF2 OR HEY1) HAIRY NM 012258 ND ENHANCER OF SPLIT RELATED-1 HEY1 PROTEIN). 4321 GN3: (NEUROG3 ORNGN3 ORATOHS OR NM 020999 TH4B) NEUROGENIN3 (ATONAL ROTEIN HOMOLOG5) (HELIX-LOOP HELIX PROTEIN MATH-4B) (MATH4B) (RELAX). 4331 RACK17: (OLIG2 OR BHLHB1 OR PRKCBP2 NM OO5806 1.18.10% ORRACK17) OLIGODENDROCYTE TRANSCRIPTION FACTOR2 (BASIC HELIX LOOP-HELIX PROTEIN CLASS B 1) (PROTEIN KINASEC-BINDING PROTEIN RACK17) (PROTEIN KINASEC BINDING PROTEIN 2). 4334 SCX: (SCX) SCLERAXIS 4398 BRACHYURY: (T) BRACHYURY PROTEIN O15178 NM OO3181 (T PROTEIN). 4418 MEF-2C: (MEF2C) MYOCYTE-SPECIFIC Q06413 NM 002397 ENEHANCER FACTOR2C. 4436 TBX1: (TBX1) T-BOX TRANSCRIPTION NM OO5992 FACTOR TBX1 (T-BOX PROTEIN 1) NM 08.0646 (TESTIS-SPECIFIC T-BOX PROTEIN). NM 080647 4446 TBX3: (TBX3) T-BOX TRANSCRIPTION NM OO5996 1.31.11% FACTORTBX3 (T-BOX PROTEIN3). NM O16569 4448 TBX5 1: (TBX5) T-BOX TRANSCRIPTION NM OOO192 FACTORTBX5 (T-BOX PROTEIN5). NM 080717 NM 181486 4528 CXCL12: (CXCL12 OR SDF1) STROMAL P48061 NM OOO609 CELL-DERIVED FACTOR 1 PRECURSOR (SDF-1) (CXCL12) (PRE-B CELL GROWTH STIMULATING FACTOR) (PBSF) (12-O- US 2008/O 159999 A1 Jul. 3, 2008 35

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 TETRADECANOYLPHORBOL 13-ACETATE REPRESSED PROTEIN 1) (TPAR1) (THYMIC LYMPHOMA CELL STIMULATING FACTOR) (TLSF). 4683 FGFR1. 1 HUMAN: (FGFR1 ORFLG OR Q02063 Q02065 NM OOO604 FGFBR OR FLT2) BASIC FIBROBLAST Q14306 Q14307 NM O15850 GROWTH FACTOR RECEPTOR1 Q8N685 P11362 NM 023105 PRECURSOR (BFGF-R) EC 2.7.1.112) (FMS P17049 NM 023106 LIKE TYROSINE KINASE-2) (C-FGR) NM 023107 (BFGFR) (CD331 ANTIGEN). NM 0231.08 NM O 4690 EGF: (EGF) PRO-EPIDERMAL GROWTH PO1133 NM OO1963 FACTOR PRECURSOR (EGF) CONTAINS: EPIDERMAL GROWTH FACTOR (UROGASTRONE). 4693 EGFR 1: (EGFR OR ERBB1) EPIDERMAL NM OO5228 1.61.24% GROWTH FACTOR RECEPTOR PRECURSOR (EC 2.7.1.112) (RECEPTOR PROTEIN TYROSINE KINASE ERBB-1).

4695 FN1 EIIIA: (FN1 ORFN) FIBRONECTIN NM 002026 PRECURSOR (FIBRONECTIN EIIIA NM 212475 DOMAIN). NM 212478 NM 212482

4696 ENOS: (NOS3) NITRIC-OXIDE SYNTHASE, NMOOO603 O.91.17% ENDOTHELLAL (EC 1.14.13.39) (EC-NOS) (NOS, TYPE III) (NOSIII) (ENDOTHELIAL NOS) (ENOS)(CONSTITUTIVE NOS) (CNOS). 4699 EDN1: (EDN1) ENDOTHELIN-1 PRECURSOR P05305 NM OO1955 (ET-1). 4701 EDN2: (EDN2) ENDOTHELIN-2 PRECURSOR NM OO1956 (ET-2) (VASOACTIVE INTESTINAL CONTRACTOR) (VIC). 4705 GFAP 1 HUMAN: (GFAP) GLIAL NM 002055 FIBRILLARY ACIDIC PROTEIN, ASTROCYTE (GFAP).

4711 HGF: (HGF OR HPTA) HEPATOCYTE NM OOO601 GROWTH FACTOR PRECURSOR (SCATTER FACTOR) (SF) (HEPATOPOEITINA).

4715 SERPINH1-SERPINH2: (SERPINH1 ORCBP1 NM OO1235 0.64.10% OR HSP47) HEAT SHOCKPROTEIN 47 COLLAGEN BINDING PROTEIN 1 (CBP1) (COLLIGIN 1) (SERPINH2 OR CBP2) (COLLAGEN-BINDING PROTEIN 2 PRECURSOR) (COLLIGIN 2) (RHEUMATOID ARTHRITIS RELATED ANTIGEN RA-A47). 4727 IGF1R: (IGF1R) INSULIN-LIKE GROWTH P08069 NM OOO875 1.26.22% FACTORI RECEPTOR PRECURSOR (EC 2.7.1.112) (CD221 ANTIGEN). 4736 LIF: (LIF OR HILDA) LEUKEMIA NM 002309 O.35.13% INHIBITORY FACTOR PRECURSOR (LIF) (DIFFERENTIATION-STIMULATING FACTOR) (DFACTOR) (MELANOMA DERIVED LPL INHIBITOR) (MLPLI) (CHOLINERGIC NEURONAL DIFFERENTIATION FACTOR). 4739 LIFR: (LIFR) LEUKEMIA INHIBITORY NM 002310 FACTOR RECEPTOR PRECURSOR (LIF-R) (CD118 ANTIGEN) (LIFRA).

US 2008/O 159999 A1 Jul. 3, 2008 37

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 4923 TFCOUP1: (TFCOUP1 ORNR2F1 OR P10589 NM OO5654 1.47 % ERBAL3 OREAR3) COUPTRANSCRIPTION FACTOR 1 (COUP-TF1) (COUP-TF I) (V- ERBARELATED PROTEIN EAR-3). 4978 CNTF-ZFP91. 1: (CNTF) CILLARY NM 000614 NEUROTROPHICFACTOR (ZFP91) (ZINC NM 170768 FINGER PROTEINZFP91) (PZF) (ZINK FINGER PROTEIN PZF). 4982 CTF1: (CTF1) CARDIOTROPHIN-1 (CT-1). Q16619 NM OO1330 4986 HBEGF: (HBEGF OR DTR OR HEGFL) Q99075 NM OO1945 O.40.20% HEPARIN-BINDING EGF-LIKE GROWTH FACTOR PRECURSOR (HB-EGF) (HBEGF) (DIPHTERIA TOXIN RECEPTOR) (DT-R). 4990 NRG1: (NRG1 OR HGLORNDF OR HRGA NM O13956 ORGGF OR SMDF) PRO-N EUREGULIN-1 NM O13957 PRECURSOR (PRO-NRG1) CONTAINS: NM O13964 NEUREGULIN-1 (NEU DIF FERENTIATION FACTOR) (HEREGULIN) (HRG) (BREAST CANCER CELL DIFFERENTIATION FACTOR P45) (ACETYLCHOLIN ECEPTOR (NDUCING ACTIVITY) (ARIA 4995 NRG3: (NRG3) PRO-NE UR EGULIN-3 NM 001010848 1.06 % PRECURSOR (PRO-NRG3) CONTAINS: NEUREGULIN-3 (NRG-3). 4999 NRG4: (NRG4) PRO-NE UR EGULIN-4, SHORT NM 138573 SOFORM (PRO-NRG4) CONTAINS: NEUREGULIN-4 (NRG-4). SOOO NRG2 1: (NRG2 OR NTAK) PRO O14511 NM OO4883 NEUREGULIN-2, MEMBRANE-BOUND NM O13981 SOFORM PRECURSOR (PRO-NRG2) NMO13982 CONTAINS: NEUREGULIN-2 (NRG-2) NM O13983 (NEURAL- AND THYM US DERIVED ACTIVATOR FOR ERBB KINASES) (NTAK) (DIVERGENT OF NEUREGULIN-1) (DON-1)). SOO4 SMAD1: (MADH1 OR SMAD1 OR MADR1 Q15797 Q16636 NM OO5900 O.80.4% ORBSP1) MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 1 (SMAD 1) (MOTHERS AGAINST DPP HOMOLOG 1) (MAD-RELATED PROTEIN 1) (TRANSFORMING GROWTH FACTOR-BETA SIGNALING PROTEIN-1) (BSP-1) (HSMAD1) (JV4-1). SOO6 SMAD5: (MADH5 OR SMAD5) MOTHERS NM OO5903 AGAINST DECAPENTAPLEGIC HOMOLOG 5 (SMAD 5) (MOTHERS AGAINST DPP HOMOLOG5) (SMAD5) (HSMAD5) (JV5-1). SO10 SMAD9: (MADH9 OR SMAD9 OR MADH6 O15198O14989 NM OO5905 ORSMAD8) MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 9 (SMAD 9) (MOTHERS AGAINST DPP HOMOLOG 9) (SMAD9) (MADH6) (SMAD8). SO14 AKT1: (AKT1 OR RAC OR PKB) RAC-ALPHA NM 001014431 1.40.5% SERINETHREONINE KINASE (EC 2.7.1. ) NM 001014432 (RAC-PK-ALPHA) (PROTEIN KINASEB) (PKB) (C-AKT). SO16 ATM 1: (ATM) SERINE-PROTEIN KINASE Q16551 Q12758 NM 000051 O45.6% ATM (EC 2.7.1.37) (ATAXIA Q9NPO2 NM 138292 TELANGIECTASIA MUTATED) (A-T, Q9UCX7 MUTATED) (ATDC). O15429 Q93.007 Q13315 SO18 CTNNB1: (CTNNB1 ORCTNNB) BETA P35222 NM OO1904 CATENIN. Q8NEW9 Q8NI94 Q9H391 5032 MDM2: (MDM2). UBIQUITIN-PROTEIN Q00987 Q13226 NM 002392 LIGASE E3 MDM2 (EC 6.3.2. ) (P53-BINDING Q13297 Q13298 PROTEIN MDM2) (ONCOPROTEIN MDM2) Q13299 Q13300 (DOUBLE MINUTE 2 PROTEIN) (HDM2). Q13301 Q9UGI3 Q9UMT8 Q SO36 MYB: (MYB) MYB PROTO-ONCOGENE Q14023 P10242 NM OO5375 PROTEIN (C-MYB). Q14024 Q9UE83 P78525 US 2008/O 159999 A1 Jul. 3, 2008 38

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 P78526 P78392 P78391 5040 PTCH: (PTCH) PATCHED PROTEIN Q13635 Q13463 NM 000264 OMOLOG 1 (PTC1) (PTC). QSVZCO SO42 PTEN1-PTENP1 HUMAN: ((PTEN OR O14781 P60484 NM 000314 1.07 % MMAC1 OR TEP1) AND (PTEN2 OR PTENP1 ORPTH2)) PHOSPHATIDYLINOSITOL-3,4,5- TRISPHOSPHATE3-PHOSPHATASEAND DUAL-SPECIFICITY PROTEIN PHOSPHATASE PTEN (EC 3.1.3.67) (EC 3. 1.3.16) (EC 3.1.3.48) (PHOSPHATASE AND TENSIN HOMOLOG) (MU SO44 RB: (RB1 OR RB-1) RETINOBLASTOMA NM OOO321 ASSOCIATED PROTEIN (PP110) (P105-RB) (RB). 5056 GF1 1: (IGF1 OR IBP1) INSULIN-LIKE NM 000618 GROWTH FACTORIA PRECURSOR(IGF-IA) (SOMATOMEDINC) (INSULIN-LIKE GROWTH FACTOR IB PRECURSOR) (IGF B). 5131 D K1: (CDC2) CELL DIVISION CONTROL O60764 PO6493 NM OO1786 ROTEIN 2 HOMOLOG (EC 2.7.1. ) (P34 NM 033379 ROTEIN KINASE) (CYCLIN-DEPENDENT (NASE 1) (CDK1). 5137 K4: (CDK4) CELL DIVISION PROTEIN NM 000075 (NASE4 (EC 2.7.1. ) (CYCLIN-DEPENDENT (NASE4) (PSK-J3). S149 KN2A 1: (CDKN2A ORCDKN2) CYCLIN NM OOOO77 PENDENT KINASE 4 INHIBITORA NM 058195 CDK4I) (P16-INK4) (P16-INK4A) NM O58197 ULTIPLE TUMOR SUPPRESSOR1) CS1) (P14ARFOR ARF) (CELL CYCLE GULATOR). 5153 N2B: (CDKN2B ORMTS2) CYCLIN NM 004936 P PENDENT KINASE 4 INHIBITORB (P14 NM O78487 (NK4B) (P15-INK4B) (MULTIPLE TUMOR S U PPRESSOR2) (MTS2). 5159 KN2D. (CDKN2D) CYCLIN-DEPENDENT NM OO1800 (NASE 4 INHIBITORD (P19-INK4D). NM O79421 5171 BB2: (ERBB2 OR HER2 ORNGL OR NEU) NM 001005862 1.24.21% C EPTOR PROTEIN-TYROSINEKINASE NM 004448 BB-2 PRECURSOR (EC 2.7.1.112) ts 85ERBB2) (NEUPROTO-ONCOGENE) (C- E BB-2) (TYROSINE KINASE-TYPE CELL S s RFACE RECEPTOR HER2) (MLN 19) (C D 340 ANTIGEN). 5.177 : (FGF1 ORFGFA) HEPARIN-BINDING P05230 PO75O2 NM 000800 1.02 % GROWTH FACTOR 1 PRECURSOR(HBGF-1) NM 033136 (ACIDIC FIBROBLAST GROWTH FACTOR) NM 033137 (AFGF) (BETA-ENDOTHELIAL CELL GROWTH FACTOR) (ECGF-BETA). FGF10: ( FGF10) FIBROBLAST GROWTH NM 004.465 FACTOR-10 PRECURSOR (FGF-10) (KERATINOCYTE GROWTH FACTOR2). F11: (FGF11 ORFHF3) FIBROBLAST NM 004112 GROWTH FACTOR-11 (FGF-11) (FIBROBLAST GROWTH FACTOR HOMOLOGOUS FACTOR3) (FHF-3) FGF14: (FGF14 ORFHF4) FIBROBLAST NM OO4115 GROWTH FACTOR-14 (FGF-14) NM 175929 (FIBROBLAST GROWTH FACTOR HOMOLOGOUS FACTOR4) (FHF-4). FGF16: (FGF16) FIBROBLAST GROWTH NM OO3868 FACTOR-16 (FGF-16). FGF19 HUMAN: (FGF19) FIBROBLAST O95750 NM OO5117 1.37.13% GROWTH FACTOR-19 PRECURSOR(FGF FGF3: (FGF3) FIBROBLAST GROWTH P11487 NM OO5247 FACTOR3 INT2 PROTO-ONCOGENE PR TEIN PRECURSOR) FGF5: (FGF5) FIBROBLAST GROWTH NM 004464 FACTOR-5 PRECURSOR (FGF-5) (HBGF-5). NM 033143

US 2008/O 159999 A1 Jul. 3, 2008 40

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 5360 APB: (APOB) APOLIPOPROTEIN B-100 P784.79 P7848O NM OOO384 PRECURSOR (APO B-100) (CONTAINS: P784.81 Q13779 APOLIPOPROTEIN B-48 (APO B-48)). Q13785 Q13786 Q13788 Q9UMNO PO4114 O 5366 APC3: (APOC3) APOLIPOPROTEINC-III P02656 Q08E83 NM 000040 PRECURSOR (APO-CIII). Q6Q786 5434 EDN3: (EDN3) ENDOTHELIN-3 PRECURSOR P14138 Q03229 NM 000114 (ET-3). NM 207032 NM 207033 NM 207034 5439 FABP4: (FABP4 ORAP2 OR FABA) FATTY P15090 NM OO1442 ACID-BINDING PROTEIN, ADIPOCYTE (AFABP) (ADIPOCYTE LIPID-BINDING PROTEIN) (ALBP) (A-FABP) (P2 DI POCYTE PROTEIN) (MYELIN P2 ROTEIN HOMOLOG) (3T3-L1 LIPID NDING PROTEIN) (422 PROTEIN) (P15). 5440 BA BP7: (FABP7 ORFABB ORFABPB OR O15540 O14951 NM OO1446 BP ORMRG) FATTY ACID-BINDING Q6IAU7 OTEIN, BRAIN (B-FABP) (BRAIN LIPID NDINGPROTEIN) (BLBP) (MAMMARY (VED GROWTH INHIBITOR RELATED). 5442 : (FABP5 OR MAL1 ORKLBP OR Q01469 NM OO1444 1.10.7% E) FATTY ACID-BINDING PROTEIN, C DERMAL (E-FABP) (PSORIASIS IATED FATTY ACID-BINDING ROT N HOMOLOG) (PA-FABP). 5446 A BI FABP2) FATTY ACID-BINDING P12104 NMOOO134 N, INTESTINAL (I-FABP) (FABPI). S456 s 2. : (FGF2 ORFGFB) HEPARIN- PO9038 NM OO2006 NG GROWTH FACTOR2 PRECURSOR F-2) (BASIC FIBROBLAST GROWTH (OR) (BFGF) (PROSTATROPIN). S498 LR: (VLDLRORLDVR) VERY LOW- P98155 NM 003383 DENSITY LIPOPROTEIN RECEPTOR Q5VVF6 PRECURSOR (VLDL RECEPTOR). SS44 LEP 2: (LEPOROB) LEPTIN PRECURSOR P41159 O15158 NM OOO230 1.43 —% (OBESITY FACTOR) (OBESE PROTEIN). Q56A88 5574 PGH2: (PTGS2 OR COX2) PROSTAGLANDIN P35354 Q16876 NM OOO963 O.31.8% G/HSYNTHASE 2 PRECURSOR (EC 14.99.1) (CYCLOOXYGENASE-2) (COX-2) (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASE 2) (PROSTAGLANDIN H2SYNTHASE 2) (PGH SYNTHASE 2) (PGHS-2) (PHS II) (PTGS2). 6118 COX7A2: (COX7A2 OR COX7AL) P14406 Q5TF59 NM OO1865 1.17.79% CYTOCHROME COXIDASE POLYPEPTIDE Q6FGI2 VIIA-LIVER/HEART, MITOCHONDRIAL PRECURSOR (EC 1.9.3.1) (CYTOCHROMEC OXIDASE SUBUNIT VIIA-L). 6124 CPS1: (CPS1) CARBAMOYL-PHOSPHATE Q7ZSIS P31327 NM OO1875 SYNTHASE AMMONIA), O43774 MITOCHONDRIAL PRECURSOR (EC 6.3.4.16) (CARBAMOYL-PHOSPHATE SYNTHETASE I) (CPSASE I). 6146 GCK: (GCK) HEXOKINASE D, PANCREATIC Q05810 P35557 NM OOO162 1.52.24% ISOZYME (EC 2.7.1.1) (HEXOKINASETYPE NM 03.3507 IV) (HK4) (GLUCOKINASE). NM 03.3508 61.94 MTHFD2: (MTGFD2 OR NMDMC) P13995 Q53G90 NM OO6636 BIFUNCTIONAL Q53GV5 METHYLENETETRAHYDROFOLATE Q53S36 DEHYDROGENASECYCLOHYDROLASE, MITOCHONDRIAL PRECURSOR INCLUDES: NAD-DEPENDENT METHYLENETETRAHYDROFOLATE DEHYDROGENASE (EC 1.5.1.15); METHENYLTETRAHYDROFOLATE CYCLOHYDROLASE (EC 3.5.4.9)). 6204 PCK2: (PCK2 OR PEPCK2) Q9BV62 NM 004.563 O.80.6% PHOSPHOENOLPYRUVATE Q16822 O43253 CARBOXYKINASE, MITOCHONDRIAL US 2008/O 159999 A1 Jul. 3, 2008 41

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 PRECURSOR GTP (EC 4.1.1.32) (PHOSPHOENOLPYRUVATE CARBOXYLASE) (PEPCK-M). 6515 AMBP: (AMBP ORITIL ORHCP)AMBP PO276OPO2759 NM OO1633 PROTEIN PRECURSOR CONTAINS: POO977 P78491 ALPHA-1-MICROGLOBULIN (PROTEIN HC) (COMPLEX-FORMING GLYCOPROTEIN HETEROGENEOUS IN CHARGE); INTER ALPEHA-TRYPSIN INHIBITORLIGHT CHAIN (ITI-LC) (BIKUNIN) (HI-30). 6887 F2: (F2) PROTHROMBIN PRECURSOR (EC POO734 NM 000506 3.4.21.5) (COAGULATION FACTOR II). 6890 F5: (F5) COAGULATION FACTORV NM OOO130 PRECURSOR (ACTIVATED PROTEIN C COFACTOR). 6893 F8C: (CF8 ORF8C) COAGULATION FACTOR NM OOO132 VIII PRECURSOR (PROCOAGULANT COMPONENT) (ANTIHEMOPHILIC FACTOR) (AHF) 7010 TTR: (TTROR PALB) TRANSTHYRETIN NM OOO371 PRECURSOR (PREALBUMIN) (TBPA) (TTR) (ATTR). 7043 CYP3A4 HUMAN: (CYP3A4) NM O17460 CYTOCHROME P450 3A4 (EC 1.14.14.1) (CYPIIIA4) (NIFEDIPINE OXIDASE) (NF-25) (P450-PCN1). 7082 CCT8: (CCT8 ORCCTQ) T-COMPLEX P50990 NM OO6585 PROTEIN 1, THETA SUBUNIT (TCP-1- THETA) (CCTTHETA) (KIAAO002). 7088 CDC25B: (CDC25B ORCDC25HU2) M NM 004358 O.75.36% PHASE INDUCER PHOSPHATASE 2 (EC NM O21872 3.1.3.48). NM O21873

7091 CDC25C: (CDC25C) M-PHASE INDUCER NM 0228.09 PHOSPHATASE 3 (EC 3.1.3.48).

7346 PSMA2: (PSMA2 OR PSC3) PROTEASOME NM OO2787 1.11.11% SUBUNITALPHATYPE 2 (EC 3.4.25.1) (PROTEASOME COMPONENT C3) (MACROPAIN SUBUNIT C3) (MULTICATALYTIC ENDOPEPTIDASE COMPLEX SUBUNIT C3). 7352 PSMA3: (PSMA3 ORPSC8) PROTEASOME NM OO2788 1.01.2% SUBUNITALPHATYPE 3 (EC 3.499.46) NM 152132 (PROTEASOME COMPONENT C8) (MACROPAIN SUBUNIT C8) (MULTICATALYTIC ENDOPEPTIDASE COMPLEX SUBUNIT C8) (INGENSIN). 7382 ABCC8: (ABCC8 OR SUR1 ORSUR) (ABC Q09428 O75948 NM OOO352 TRANSPORTER) SULFONYLUREA Q16583 RECEPTOR 1. 7523 ABCG2: (ABCG2 OR ABCP OR BCRP OR NM 004.827 BCRP1) ATP-BINDING CASSETTE, SUB FAMILY G, MEMBER2 (PLACENTA SPECIFICATP-BINDING CASSETTE TRANSPORTER) (BREAST CANCER RESISTANCE PROTEIN) (MITOXANTRONE RESISTANCE-ASSOCIATED PROTEIN) (CD338 ANTIGEN) (CDW338). 7634 EMX-2: (EMX2 OR EMX-2) HOMEOBOX NM 004.098 PROTEIN EMX2 (FRAGMENT) 7804 KRT14: (KRT14) KERATIN, TYPE I NM 000526 1.23 -% CYTOSKELETAL 14 (CYTOKERATIN 14) (K14) (CK14). US 2008/O 159999 A1 Jul. 3, 2008

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 Q9UBN3 Q9UCY4 7807 KRT17: (KRT17) KERATIN, TYPE I Q04695 NM 000422 CYTOSKELETAL 17 (CYTOKERATIN 17) (K17) (CK 17) (39.1) (VERSION 1). 7837 CDH2: (CDH2ORCDHN OR NCAD) P19022 Q14923 NM OO1792 ADHERIN-2 PRECURSOR (NEURAL ADHERIN) (N-CADHERIN) (CD325 NTIGEN) (CDW325). 7873 DC1: (ODC1) ORNITHINE NM 002539 1.42.3% ECARBOXYLASE (EC 4.1.1.17) (ODC). 7924 RAC1: (RAC1) RAS-RELATED C3 NM 018890 1.00.15% BOTULINUM TOXIN SUBSTRATE 1 (P21 RAC1) (RAS-LIKE PROTEIN TC25). 7939 RHOA: (ARHA OR ARH12 OR RHOAOR P61586 NM OO1664 1.15.7% RHO12) TRANSFORMING PROTEIN RHOA (H12). 7951 RPL7A: (RPL7A OR SURF3 OR SURF-3)6OS P11518 P62424 NM OOO972 1.28.9% RIBOSOMAL PROTEIN L7A (SURFEIT LOCUS PROTEIN3) (PLA-X POLYPEPTIDE). 7987 ABCC9: (ABCC9 OR SUR2) ATP-BINDING O60707 O60706 CASSETTETRANSPORTER SUB-FAMILY C MEMBER 9 (SULFONYLUREA RECEPTOR 2). 7996 TK1: (TK1) THYMIDINE KINASE, NM OO3258 CYTOSOLIC (EC 2.7.1.21). AFP: (AFP) ALPHA-FETOPROTEIN NM 001134 PRECURSOR (ALPHA-FETOGLOBULIN) (ALPHA-1-FETOPROTEIN). 8071 CTNNA1: (CTNNA1) ALPHA-1 CATENIN P35221 Q12795 NMOO1903 O.87.10% (CADHERIN-ASSOCIATED PROTEIN) (ALPHAE-CATENIN) (NY-REN-13 ANTIGEN). 808O ENO2: (ENO2) GAMMA ENOLASE (EC NM OO1975 O.85.24% 4.2.1.11) (2-PHOSPHO-D-GLYCERATE HYDRO-LYASE) (NEURAL ENOLASE) (NEURON-SPECIFICENOLASE) (NSE) (ENOLASE 2). 8188 RBL2: (RBL2 OR RB2) RETINOBLASTOMA Q08999 Q15073 NM OO5611 KE PROTEIN 2 (130 KDA Q928.12 Q16084 ETINOBLASTOMA-ASSOCIATED ROTEIN) (PRB2) (P130) (RBR-2). 8612 RF1: (TRF1 ORTRF) TELOMERIC REPEAT NM OO3218 NDING FACTOR 1. NM O17489 TB24: (ZBTB24 OR KIAAO441 ORZNF450) NM 014797 NCFINGERAND BTB DOMAIN ONTAINING PROTEIN 24 (ZINC FINGER ROTEIN 450) (BIF1) (BMP-INDUCED ACTOR 1). 9037 AG1: (JAG1 ORJAGL1) JAGGED 1 P78504 O14902 NM 000214 PRECURSOR (JAGGED1) (HJ1) (NOTCH O15122 Q15816 LIGAND JAGGED 1) (CD339 ANTIGEN). 9046 NOTCH1: (NOTCH1 ORTAN1) P46531 NM O17617 NEUROGENICLOCUS NOTCH PROTEIN HOMOLOG 1 PRECURSOR 9060 ACTG2: (ACTG2 ORACTA3 ORACTSG) NM OO1615 ACTIN, GAMMA-ENT ERICSMOOTH MUSCLE (ALPHA-AC CIN3). 9099 FGFR3: (FGFR3 ORJT K4) FIBROBLAST P22607 Q16608 NM 000142 GROWTH FACTOR RE CEPTOR 3 Q14308 Q16294 NM 022965 PRECURSOR (EC 2.7.1 0.1) (FGFR-3) (CD333 ANTIGEN). 9102 FLN1: (FLNA OR FLN OR FLN) FILAMINA P21333 NM OO1456 O.88.3% (ALPHA-FILAMIN) (F LAMIN 1) (ENDOTHELIAL ACTIN-BINDING PROTEIN) (ABP-280) (NONMUSCLE FILAMIN). 9132 MYH11: (MYH11 OR KIAAO866) MYOSIN-11 P35749 P78422 NM OO2474 (MYOSIN HEAVY CHAIN, SMOOTH O94944 OOO396 NM 022844 MUSCLE ISOFORM) (SMMHC). 9144 SERPINF1: (SERPINF1 OR PEDF OR SDF3) NM 002615 1.11.13% PIGMENTEPITHELIUM-DERIVED FACTOR PRECURSOR (PEDF) (EPC-1) (STROMAL US 2008/O 159999 A1 Jul. 3, 2008 43

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 CELL-DERIVED FACTOR3) (SDF-3) (CASPIN). SLC2A1: (SLC2A1 OR GLUT1) GLUCOSE P11166 O75535 NM OO6516 0.31.14% TRANSPORTERTYPE 1, ERYTHROCYTEBRAIN. 92.25 ECE1: (ECE1) ENDOTHELIN-CONVERTING NM 001397 O.87.11% ENZYME1 (EC 3.4.24.71) (ECE-1).

9249 GGT5: (GGT5 ORGGTLA1) GAMMA NM 004121 1.04.10% GLUTAMYLTRANSPEPTIDASES PRECURSOR (EC 2.3.2.2) (GAMMA GLUTAMYLTRANSFERASE 5) (GGT-REL). 9261 LDHB: (LDHB) L-LACTATE PO7195 NM 002300 1.64.12% DEHYDROGENASE H CHAIN (EC 1.1.1.27) L-LACTATE DEHYDROGENASEB CHAIN (EC 1.1.1.27) (LDH-B) (LDH HEART SUBUNIT) (LDH-H). BMP10: (BMP10) BONE MORPHOGENETIC O95393 NM O14482 PROTEIN 10. GDF2: (GDF2 OR BMP9) NM 016204 1.59.24% GROWTHADIFFERENTIATION FACTOR 2 PRECURSOR (GDF-2) (BONE MORPHOGENETIC PROTEIN 9) (BMP-9). 93.11 CBFA1: (RUNX2 OR CBFA1 OR AML3 OR Q13950 O14615 NM 001015051 1.67.18% PEBP2A OR OSF2) RUNT-RELATED O95181 O14614 NMOO1024630 TRANSCRIPTION FACTOR2 (CORE NM 004348 BINDING FACTOR, ALPHA 1 SUBUNIT) (CBF-ALPHA1) (ACUTE MYELOID LEUKEMLA 3 PROTEIN) (ONCOGENE AML 3) (POLYOMAVIRUS ENHANCERBINDING PROTEIN 2 ALPHAA SUBUNIT). 93.14 CRABP2: (CRABP2) RETINOIC ACID NM OO1878 BINDING PROTEIN II, CELLULAR (CRABP ). 9326 ONECUT1: (ONECUT1 OR HNF6A OR HNF6) NM 004498 HEPATOCYTE NUCLEAR FACTOR 6 (HNF 6) (ONE CUT DOMAIN FAMILY MEMBER ). 9338 HOXA2: (HOXA2) HOMEOBOX PROTEIN O43364 NM OO6735 HOX-A2. 9362 PRRX1: (PRRX1 ORPMX1 OR PRX1) PS4821 O60807 NM OO6902 O.75.11% PAIRED MESODERMHOMEOBOX NM O22716 PROTEIN 1 (PRX-1) (PAIRED RELATED HOMEOBOX PROTEIN 1) (HOMEOBOX PROTEIN PHOX1). 9377 RAD17: (RAD17 OR R24L) CELL CYCLE NM 002873 CHECKPOINT PROTEINRAD17 (HRAD17) NM 133338 (RF-C/ACTIVATOR 1 HOMOLOG) (HRAD17) NM 133339 (DKFZP434A1135). NM 133341 NM 133342 NM 133343 NM 1 9386 RBL1: (RBL1) RETINOBLASTOMA-LIKE NM 002895 PROTEIN 1 (107 KDARETINOBLASTOMA ASSOCIATED PROTEIN) (PRB1) (P107). SOX9: (SOX9) TRANSCRIPTION FACTOR NM OOO346 SOX-9. 9422 WNT1OB: (WNT1 OB ORWNT10 ORWNT12 NM OO3394 ORWNT-10B) WNT-10B PROTEIN PRECURSOR(WNT-12). WNT11: (WNT11 ORWNT-11) WNT-11 NM 004626 1.18 % PROTEIN PRECURSOR 9437 WNT2: (WNT2 OR IRP ORWNT-2) WNT-2 NM OO3391 PROTEIN PRECURSOR(IRP PROTEIN) (INT 1 RELATED PROTEIN). 9443 WNT3: (WNT3 ORWNT-3 OR INT4) WNT-3 NM 030753 PROTO-ONCOGENE PROTEIN PRECURSOR. US 2008/O 159999 A1 Jul. 3, 2008 44

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 94.49 WNT4: (WNT4 ORWNT-4) WNT-4 PROTEIN NM O30761 PRECURSOR (UNQ426/PRO864).

9452 WNT5A: (WNTSA ORWNT-5A) WNT-5A NM OO3392 PROTEIN PRECURSOR. 9456 WNTSB: (WNTSB ORWNT-5B) WNT-5B NM 030775 1.05.20% PROTEIN PRECURSOR. NM 0326.42 9459 WNT6: (WNT6 ORWNT-6) WNT-6 PROTEIN PRECURSOR. 9461 WNT7A: (WNT7A ORWNT-7A) WNT-7A NM 004625 PROTEIN PRECURSOR. 95.72 ELOVL6: (ELOVL6 OR BALDSPOT OR FAE NM 024090 OR RELO2) LONG-CHAIN FATTY-ACYL ELONGASE (ELOVL6 PROTEIN) (FATTY ACID ELONGASE 2) (MYELINATION ASSOCIATED SUR4-LIKE PROTEIN) (FLJ23378). 9638 F2R: (F2R OR PAR1 OR TRORCF2R) NM OO1992 1.27.5% PROTEINASE ACTIVATED RECEPTOR1 PRECURSOR (PAR-1) (THROMBIN RECEPTOR) (COAGULATION FACTOR II RECEPTOR). 9663 H ERMES: (HERMES OR RBPMS) RNA NM OO6867 O.97.14% B NDING PROTEIN WITH MULTIPLE SPLICING (RBP-MS). 97.07 NRP1: (NRP1 OR NRP ORVEGF165R) NM OO3873 1.23.44% NEUROPILIN-1 PRECURSOR (VASCULAR ENDOTHELLAL CELL GROWTH FACTOR 65 RECEPTOR) (CD304 ANTIGEN). 9713 PAFAH1B1: (PAFAH1B1 OR PAFAHAOR NM 000430 O.91.9% LIS1 ORMDCR) PLATELET-ACTIVATING FACTORACETYLEHYDROLASEIBALPHA SUBUNIT (EC 3.1.1.47) (PAF ACETYLHYDROLASE 45 KDA SUBUNIT) (PAF-AH 45 KDA SUBUNIT) (PAF-AH ALPHA) (PAFAHALPHA) (LISSENCEPHALY-1 PROTEIN) (LIS-1). 9992 MGST1: (MGST1 ORMGST OR GST12) P1062O NM O2O300 GLUTATHIONES-TRANSFERASE, NM 145764 MICROSOMAL (EC 2.5.1.18). NM 145791 NM 145792 10164 SLAT8A: (SLAT8A OR SLAT8) ALPHA-N- Q93064. Q92185 NM OO3O34 ACETYL-NEURAMINNIDEALPHA-2,8- SLALYLTRANSFERASE (EC 2.499.8) (GANGLIOSIDE GD3/GT3 SYNTHASE) (SIALYLTRANSFERASE8) (ST8SIAI). 10265 ANXA2: (ANXA2 OR ANX2) ANNEXIN II NM OO1002857 0.65.10% (LIPOCORTIN II) (CALPACTIN I HEAVY NM OO1002858 CHAIN) (CHROMOBINDIN 8) (P36) NM 004039 (PROTEIN I) (PLACENTAL ANTICOAGULANT PROTEIN IV) (PAP-IV). 1045S PEG1-MEST: (PEG1/MEST) PEG1/MEST O15007 O14973 NM O02402 1.27.6% PROTEIN (MESODERM SPECIFIC Q92571 NM 177524 TRANSCRIPT (MOUSE) HOMOLOG) NM 177525 (HYPOTHETICAL 38.8 KDA PROTEIN) (UNKNOWN) (PROTEINFORMGC: 20321). 10467 PLCB4: (PLCB4) PHOSPHOLIPASEC BETA NM OOO933 4. NM 182797

10470 PLCE: (PLCE OR PLCE1 OR PLC-EPSILON) NM 016341 PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE CPLC-EPSILON (KIAA1516) (PANCREAS-ENRICHED PHOSPHOLIPASEC) (FLJ12481). US 2008/O 159999 A1 Jul. 3, 2008 45

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 10934 CHEK1: (CHEK1 ORCHK1) O14757 NM OO1274 SERINETHREONINE-PROTEINKINASE CHK1 (EC 2.7.1. ) CHECKPOINT KINASE 1. 10937 CHEK2: (CHEK2 ORCHK2) NM 007194 SERINETHREONINE-PROTEINKINASE NM 145862 CHK2 (EC 2.7.1. ) (CDS1).

O970 FZD1 2: (FZD1) FRIZZLED 1 PRECURSOR NM 003505 (FRIZZLED-1) (FZ-1) (HFZ1) (FZE1) (RFZ1) (MFZ1). O985 HMGB2: (HMGB2 OR HMG2) HIGH P26583 QSU072 NM 002129 MOBILITY GROUP PROTEIN HMG2 (HMG 2). O991 HUS1 + -LIKE: (HUS1 + -LIKE OR HUS1) O60921 NM OO4507 HUS1 +-LIKE PROTEIN (HUS1 (S. POMBE) CHECKPOINT HOMOLOG) (HUS1 CHECKPOINT HOMOLOG). RAD9: (RAD9) RADIO NM 004.584 ESISTANCECHEMO-RESISTANCE CELL YCLE CHECKPOINT CONTROL PROTEIN. EP1: (TEP1 ORTP1 ORTLP1) Q99973 NM 007110 ELOMERASE PROTEIN-1. TELOMERASE SSOCIATED PROTEIN TP-1. (TLP1) ELOMERASE PROTEIN COMPONENT 1. ERT: (TERT OR TRT OREST2 OR TCS1) NMOO3219 1.SS, 9-0 ELOMERASE REVERSE TRANSCRIPTASE NM 198253 (EC 2.7.7. ) (TELOMERASE CATALYTIC NM 198254 SUBUNIT) (HEST2). NM 198255 115 ITGA3 SPRIME: (ITGA3) INTEGRIN ALPHA NM 002.204 3 PRECURSOR (GALACTOPROTEIN B3) NM OO55O1 (GAPB3) (VLA-3 ALPHACHAIN) (CD49C). 151 FGFR4: (FGFR4 ORJTK2 OR TKF) Q14309 O43785 NM OO2011 FIBROBLAST GROWTH FACTOR P224.55 NM 022963 RECEPTOR4 PRECURSOR (EC 2.7.10.1) NM 213647 (FGFR-4) (CD334 ANTIGEN). 175 KRT15: (KRT15 OR KRTB) KERATIN, TYPE NM OO2275 1.10 % ICYTOSKELETAL 15 (CYTOKERATIN 15) (K15) (CK 15). 181 KRT18: (KRT18 ORCYK18) KERATIN, TYPE NM 000224 ICYTOSKELETAL 18 (CYTOKERATIN-18) NM 1991.87 (K18) (CK-18) (KERATIN-18). 204 KRT8: (KRT8 ORCYK8) KERATIN, TYPE II NM OO2273 O.39.2% CYTOSKELETAL 8 (CYTOKERATIN 8) (K8) (CK 8) (KRT2-8).

11295 CSPG4: (CSPG4 ORMCSP ORAN2 OR NM OO1897 KIAA4232 ORNG2) CHONDROITIN SULFATE PROTEOGLYCAN 4 PRECURSOR (CHONDROITIN SULFATE PROTEOGLYCAN NG2) (MELANOMA CHONDROITIN SULFATE PROTEOGLYCAN) (MELANOMA ASSOCIATED CHONDROITIN SULFATE PROTEOGLYCAN) (AN2 PROTEOGLYCAN). 11319 SILV: (SILV OR SIORPMEL17 ORD12S53E) Q16565 Q14817 NM OO6928 1.20 % MELANOCYTE PROTEINPMEL 17 Q12763 Q14448 PRECURSOR (MELANOCYTE LINEAGE P40967 SPECIFICANTIGEN GP100) (MELANOMA ASSOCIATED ME20 ANTIGEN) (ME2OMIME2OS) (ME20-MME20-S) (95 KDA MELANOCYTE-SPECIFIC SECRETED GLYCOPROTEIN). 11328 TDGF1 2 HUMAN: (TDGF1 OR CRIPTO) P51864 P13385 NM OO3212 1.58.23% AND (TDGF3 ORTDGF2)) NR 002718 TERATOCARCINOMA-DERIVED GROWTH FACTOR 1 (EPIDERMAL GROWTH FACTOR-LIKE CRIPTO PROTEIN CR1) US 2008/O 159999 A1 Jul. 3, 2008 46

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (CRIPTO-1 GROWTH FACTOR) (CRGF) (TERATOCARCINOMA-DERIVED GROWTH FACTOR2) (EPIDERMAL GROWTH FACTOR-LIKE CRIPT 11334 TPM1: (TPM1 ORTPMAORTMSA) PO9494 PO9493 NM OOO366 O.29.9% TROPOMYOSINALPHA CHAIN. P10469 Q96IK2 Q9UCY9 Q86W64 11362 LRP8: (LRP8 ORAPOER2) LOW-DENSITY O14968 Q86V27 NM 004631 1.58 % LIPOPROTEIN RECEPTOR-RELATED Q99876 NM 017522 PROTEIN 8 PRECURSOR Q9BR78 NM 033300 (APOLIPOPROTEINE RECEPTOR2). Q14114 11389 SCARB1: (SCARB1 ORCD36L1 ORCLA1) Q8WTVO NM OO5505 SCAVENGER RECEPTOR CLASS B Q6KFX4 MEMBER1 (SRB1) (SR-BI) (CD36 ANTIGEN- Q14016 LIKE 1) (CD36 AND LIMPIIANALOGOUS 1) (CLA-1) (COLLAGEN TYPE I RECEPTOR, THROMBOSPONDIN RECEPTOR-LIKE 1). 11404 CRABP1: (CRABP1 OR RBP5) RETINOIC Q6IAY7 P29762 NM 004378 ACID-BINDING PROTEIN I, CELLULAR Q8WTV5 (CRABP-I). 11635 ACVR1: (ACVR1 ORACVRLK2) ACTIVIN Q04771 NM 001105 RECEPTOR TYPE I PRECURSOR (EC 2.7.1. ) (ACTR-I) (SERINE THREONINE-PROTEIN KINASE RECEPTORR1) (SKR1) (ACTIVIN RECEPTOR-LIKE KINASE 2) (ALK-2) (TGF-B SUPERFAMILY RECEPTORTYPE I) (TSR-I). 11641 ACVR2: (ACVR2) ACTIVIN RECEPTOR Q92474 P27037 NM OO1616 TYPE II PRECURSOR (EC 2.7.1. ) (ACTR-II) Q53TH4 (ACTRIIA). Q6NWV2 11644 ACVR2B: (ACVR2B) ACTIVIN RECEPTOR Q13705 NM 001106 TYPE IIB PRECURSOR (EC 2.7.1. ) (ACTR- Q4VAVO IB). 11647 ACVRL1: (ACVRL1 ORACVRLK1 OR ALK1) P37023 NM OOOO20 SERINETHREONINE-PROTEINKINASE RECEPTOR R3 PRECURSOR (EC 2.7.1.37) (SKR3) (ACTIVIN RECEPTOR-LIKE KINASE ) (ALK-1) (TGF-B SUPERFAMILY RECEPTOR TYPE I) (TSR-I). 11683 BMP15: (BMP15 OR GDF9B) BONE Q9UMS1 NM 005448 MORPHOGENETIC PROTEIN 15 O95972 Q5JST1 PRECURSOR (BMP-15) (GROWTHDIFFERENTIATION FACTOR 9B) (GDF-9B). 11686 BMPR1A: (BMPR1A ORACVRLK3) BONE P36894 NM 004329 MORPHOGENETIC PROTEIN RECEPTOR Q8NEN8 TYPE LA PRECURSOR (EC 2.7.1. ) (SERINE THREONINE-PROTEIN KINASE RECEPTOR R5) (SKR5) (ACTIVIN RECEPTOR-LIKE KINASE 3) (ALK-3) 11689 BMPR1B: (BMPR1B ORACVRLK6) BONE P78366 OOO238 NM OO1203 MORPHOGENETIC PROTEIN RECEPTOR TYPE IB PRECURSOR (EC 2.7.11.30) (CDW293 ANTIGEN) (SERINETHREONINE PROTEIN KINASE RECEPTOR R6) (SKR6) (ACTIVIN RECEPTOR-LIKE KINASE 6) (ALK-6). 11692 BMPR2: (BMPR2) BONE MORPHOGENETIC Q16569 Q13873 NM 001204 PROTEIN RECEPTOR TYPE II PRECURSOR NM 033346 (EC 2.7.1. ) (BMPTYPE II RECEPTOR) (BMPR-II). 11698 CD164: (CD164 ORMMGC-24) PUTATIVE Q04900 Q5JSU6 NM OO6016 0.61.11% MUCIN CORE PROTEIN 24 PRECURSOR (MULTI-GLYCOSYLATED CORE PROTEIN 24) (MGC-24) (MUC-24) (CD164 ANTIGEN) (CELL-SURFACE SIALOMUCINMGC-24) (ENDOLYN PRECURSOR). 11701 CD44 EX16-20 HUMAN: (CD44 ORLHR) Q16066 Q16522 NM 000610 107.5% CD44 ANTIGEN PRECURSOR P16070 P22511 NM OO1 OO1389 (PHAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q04858 Q13419 NM 001001390 (HUTCH-I) (EXTRACELLULAR MATRIX Q13957 Q13958 NM 001001391 RECEPTOR-III) (ECMR-III) (GP90 Q13959 Q NM 001001392 LYMPHOCYTE HOMING-ADHESION US 2008/O 159999 A1 Jul. 3, 2008 47

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 RECEPTOR) (HERMES ANTIGEN) (HYALURONATE RECEPTOR) (HEPARAN SULFATE PROTE 11704 CD44 EX13-15 HUMAN: (CD44 ORLHR) P16070 P22511 NM 000610 CD44 ANTIGEN PRECURSOR Q04858 Q13419 NM OO1OO1389 (PHAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q13957 Q13958 NM 001001390 (HUTCH-I) (EXTRACELLULAR MATRIX Q13959 Q13960 RECEPTOR-III) (ECMR-III) (GP90 Q13961 Q LYMPHOCYTE HOMING-ADHESION RECEPTOR) (HERMES ANTIGEN) (HYALURONATE RECEPTOR) (HEPARAN SULFATE PROTE 11707 CD44 EX3-5 HUMAN: (CD44 ORLHR) CD44 P16070 P22511 NM 000610 1.08.6% ANTIGEN PRECURSOR (PHAGOCYTIC Q04858 Q13419 NM OO1 OO1389 GLYCOPROTEIN I) (PGP-1) (HUTCH-I) Q13957 Q13958 NM 001001390 (EXTRACELLULAR MATRIX RECEPTOR Q13959 Q13960 NM 001001391 III) (ECMR-III) (GP90 LYMPHOCYTE Q13961 Q HOMING/ADHESION RECEPTOR) (HERMES ANTIGEN) (HYALURONATE RECEPTOR) (HEPARAN SULFATE PROTEOG 11710 CD44 EX7-9 HUMAN: (CD44 ORLHR) CD44 P22511 Q04858 NM 000610 O.98.22% ANTIGEN PRECURSOR (PHAGOCYTIC Q13419 Q13957 NM OO1 OO1389 GLYCOPROTEIN I) (PGP-1) (HUTCH-I) Q13958 Q13959 (EXTRACELLULAR MATRIX RECEPTOR Q13960 Q13961 II) (ECMR-III) (GP90 LYMPHOCYTE Q13967 Q HOMING/ADHESION RECEPTOR) (HERMES ANTIGEN) (HYALURONATE RECEPTOR) ( HEPARAN SULFATE PROTEOG 11725 CDH3: (CDH3 ORCDHP) CADHERIN-3 P22223 NM OO1793 PRECURSOR (PLACENTAL-CADHERIN) (P- CADHERIN). 11761 EGR2: (EGR2 OR KROX20) EARLY NM OOO399 GROWTH RESPONSE PROTEIN 2 (EGR-2) KROX-20 PROTEIN) (AT591). 11767 EPHB2: (EPHB2 OR EPTH3 OR ERKORDRT NM 004442 OR HEK5) EPHRIN TYPE-B RECEPTOR 2 NM O17449 PRECURSOR (EC 2.7.1.112) (TYROSINE PROTEIN KINASE RECEPTOR EPH-3) (DRT) (RECEPTOR PROTEIN-TYROSINE KINASE HEK5) (ERK). 797 GATA2: (GATA2) ENDOTHELIAL NM 032638 1.18.10% TRANSCRIPTION FACTOR GATA-2. 804 GATA4: (GATA4) TRANSCRIPTION P43694 NM 002052 FACTOR GATA-4 (GATA BINDING FACTOR-4). 827 HHEX: (HHEXOR PRHXOR PRHOR HEX) Q03014 NM 002729 1.37.6% HOMEOBOX PROTEIN PRH (HOMEOBOX PROTEIN HEX). 878 RF2: (IRF2) INTERFERON REGULATORY Q96B99 P14316 NM 002199 1.42.23% FACTOR2 (IRF-2). 920 LMO2: (LMO2 OR RBTN2OR RHOM2 OR NM OO5574 TTG2) RHOMBOTIN-2 (CYSTEINE RICH PROTEINTTG-2) (T-CELL TRANSLOCATION PROTEIN 2) (LIM-ONLY PROTEIN 2). 953 MAP3K5: (MAP3K5 OR MAPKKKS OR Q99461 Q99683 NM OO5923 MEKK5 ORASK1) MITOGEN-ACTIVATED Q5THN3 PROTEIN KINASE KINASE KINASE5 (EC 2.7.1. ) (MAPK/ERK KINASE KINASE 5) (MEK KINASE5) (MEKK5) (APOPTOSIS SIGNAL-REGULATING KINASE 1) (ASK-1). 11986 NOG: (NOG) NOGGIN PRECURSOR. Q13253 NM OO5450 11998 PAX5: (PAX5) PAIRED BOX PROTEIN PAX-5 O75933 Q02548 NM O16734 (B-CELL SPECIFIC TRANSCRIPTION FACTOR) (BSAP). 12O34 PRKCZ: (PRKCZ OR PKC2) PROTEIN NM O02744 KINASEC, ZETA TYPE (EC 2.7.1. ) (NPKC ZETA). 12082 SELP: (SELP ORGMRP) P-SELECTIN NM OO3005 1.26 % PRECURSOR (GRANULE MEMBRANE PROTEIN 140) (GMP-140) (PADGEM) (CD62P) (LEUKOCYTE-ENDOTHELIAL CELL ADHESIONMOLECULE 3) (LECAM3). US 2008/O 159999 A1 Jul. 3, 2008

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 12085 SEMA4D: (SEMA4D ORCD100) Q7Z5S4 Q92854 NM OO6378 1.11.51% SEMAPHORIN 4D PRECURSOR (LEUKOCYTE ACTIVATION ANTIGEN CD100) (BB18) (A8) (GR3). (SEMA4D OR SEMAJ OR SEMACL2) SEMAPHORIN 4D PRECURSOR (SEMAPHORINJ) (SEMAJ) (SEMAPHORINC-LIKE2) (M-SEMA G). 12088 SEMA7A: (SEMA7A OR SEMAL ORCD108) O75326 NM OO3612 SEMAPHORIN 7APRECURSOR (SEMAPHORIN L) (SEMAL) (SEMAPHORIN K1) (SEMA K1) (JOHN-MILTON-HARGEN HUMAN BLOOD GROUP AG) (JMH BLOOD GROUP ANTIGEN) (CD108 ANTIGEN) (CDW108). 12091 SHH: (SHH) SONIC HEDGEHOG PROTEIN NM OOO193 PRECURSOR (SHH) (HHG-1) 121.69 ZNFN1A1: (ZNFN1A1 ORIKAROS ORIK1 NM OO6060 1.24f—% ORLYF1) DNA-BINDING PROTEIN IKAROS (LYMPHOID TRANSCRIPTION FACTOR LYF-1). 12281 GCG: (GCG) GLUCAGON PRECURSOR. PO1275 NM 002054 1.55.5% 123SO (NSRR: (INSRRORIRR) INSULIN O60724 P14616 NM O14215 O.93.12% RECEPTOR-RELATED PROTEIN PRECURSOR (EC 2.7.1.112) (IRR) (IR RELATED RECEPTOR). 12359 PDX1: (PDX1 ORIPF1) INSULIN PROMOTER O60594 PS2945 NM 000209 FACTOR-1 (IPF-1) (PANCREAS/DUODENUM HOMEOBOX-1) (PDX-1) (ISLET/DUODENUM HOMEOBOX-1) (IDX-1) (SOMATOSTATIN TRANSACTIVATING FACTOR-1) (STF-1) (INSULIN UPSTREAM FACTOR-1) (IUF-1) (GLUCOSE-SENSITIVE FACTOR) (GSF). 12386 SLC16A1: (SLC16A1 ORMCT1) NM OO3051 O.95.5% MONOCARBOXYLATE TRANSPORTER 1 (MCT 1). 12428 : (PCK1 OR PEPCK1) NM OO2591 1.39.10% HOSPHOENOLPYRUVATE ARBOXYKINASE, CYTOSOLIC (EC 1.1.32) (PHOSPHOENOLPYRUVATE ARBOXYLASE) (PEPCK-C). 12452 D45 EX10-11: (PTPRC ORCD45) NM 002838 EUKOCYTE COMMONANTIGEN NM 080921 RECURSOR (EC 3.1.3.48) (L-CA) (CD45 NM 080922 A.N T GEN) (T200). 12627 RIP1: (CRIP1 OR CRIP) CYSTEINE-RICH NM 001311 0.11f4% CEIN 1 (CYSTEINE-RICH INTESTINAL CEIN) (CRIP) (CYSTEINE-RICH HEART CEIN) (HCRHP). 12690 OOA11: (S100A11 OR S100C) P31949 NM OO5620 0.84.10% ALGIZZARIN (ENDOTHELIAL QSVTKO MONOCYTE-ACTIVATING POLYPEPTIDE) EMAP). 12704 D44 EX11-13 HUMAN: (CD44 ORLHR) P16070 P22511 NM 000610 D44 ANTIGEN PRECURSOR Q04858 Q13419 NM OO1OO1389 HAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q13957 Q13958 NM 001001390 UTCH-I) (EXTRACELLULAR MATRIX Q13959 Q13960 ECEPTOR-III) (ECMR-III) (GP90 Q13961 Q YMPHOCYTE HOMING-ADHESION ECEPTOR) (HERMES ANTIGEN) HYALURONATE RECEPTOR) (HEPARAN ULFATE PROTE 12707 D44 EX12-14 HUMAN: (CD44 ORLHR) Q13961 Q13967 NM 000610 1.69.52% D44 ANTIGEN PRECURSOR Q13968 Q13980 NM OO1 OO1389 HAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q15861 Q16064 NM 001001390 UTCH-I) (EXTRACELLULAR MATRIX Q16065 Q16066 ECEPTOR-III) (ECMR-III) (GP90 Q16208 Q YMPHOCYTE HOMING-ADHESION ECEPTOR) (HERMES ANTIGEN) YALURONATE RECEPTOR) (HEPARAN ULFATE PROTE 12710 D44 EX8-10 HUMAN: (CD44 ORLHR) P22511 Q04858 NM 000610 D44 ANTIGEN PRECURSOR Q13419 Q13957 NM OO1 OO1389 US 2008/O 159999 A1 Jul. 3, 2008 49

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (PHAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q13958 Q13959 (HUTCH-I) (EXTRACELLULAR MATRIX Q13960 Q13961 RECEPTOR-III) (ECMR-III) (GP90 Q13967 Q LYMPHOCYTE HOMING-ADHESION RECEPTOR) (HERMES ANTIGEN) (HYALURONATE RECEPTOR) (HEPARAN SULFATE PROTEO 12713 CD44 EX9-11 HUMAN: (CD44 ORLHR) P16070 P22511 NM 000610 CD44 ANTIGEN PRECURSOR Q04858 Q13419 NM OO1 OO1389 (PHAGOCYTIC GLYCOPROTEIN I) (PGP-1) Q13957 Q13958 (HUTCH-I) (EXTRACELLULAR MATRIX Q13959 Q13960 RECEPTOR-III) (ECMR-III) (GP90 Q13961 Q LYMPHOCYTE HOMING-ADHESION RECEPTOR) (HERMES ANTIGEN) (HYALURONATE RECEPTOR) (HEPARAN SULFATE PROTEO 12809 EGFR 2: (EGFR OR ERBB1) EPIDERMAL GROWTH FACTOR RECEPTOR PRECURSOR (EC 2.7.1.112) (RECEPTOR PROTEIN TYROSINE KINASE ERBB-1).

12917 PRKCM: (PRKCM) PROTEIN KINASEC, MU NM OO2742 TYPE (EC 2.7.1. ) (NPKC-MU). 12920 PRKCQ: (PRKCQ OR PRKCT) PROTEIN NM OO6257 1.OO.75% KINASEC, THETA TYPE (EC 2.7.1. ) (NPKC THETA). 12956 BEX2-BEX1: (BEX2) AND (BEX1 OR REX3)) NM 018476 PROTEIN BEX1 (BRAIN-EXPRESSED X NM 032621 LINKED PROTEIN 1) (PROTEIN BEX2) (BRAIN-EXPRESSEDX-LINKED PROTEIN 2) (HBEX2) (REDUCED EXPRESSION PROTEIN 3) (REX-3). 12968 CDH12: (CDH12) BRAIN-CADHERIN P55289 NM 004061 PRECURSOR (BR-CADHERIN) (CADHERIN 2) (N-CADHERIN 2) (CADHERIN, NEURAL TYPE, 2). 13004 LAVL2: (ELAVL2 OR HUB) ELAV-LIKE Q13235 NM 004.432 ROTEIN 2 (HU-ANTIGENB) (HUB) (ELAV LIKE NEURONAL PROTEIN 1) (NERVOUS YSTEM-SPECIFIC RNABINDING PROTEIN HEL-N1). 13049 HNKA: (HNKA) NEURONAL POTASSIUM NM O14379 1.33.88% CHANNEL ALPHASUBUNIT (POTASSIUM CHANNEL KV8.1) (KCNV1 OR 2700023A03RIK). 13079 CNJ4: (KCNJ4) INWARD RECTIFIER NM 004981 1.324.1% POTASSIUM CHANNEL 4 (POTASSIUM NM 152868 CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER4) (HIPPOCAMPAL (NWARD RECTIFIER) (HIR) (HRK1) (HIRK2) (KIR2.3). 13106 NTF3: (NTF3) NEUROTROPHIN-3 NM OO2527 PRECURSOR (NT-3) (NEUROTROPHIC FACTOR) (HDNF) (NERVE GROWTH FACTOR2) (NGF-2). 13118 PMX2B: (PMX2B) PAIRED MESODERM NM OO3924 1.59.44% HOMEOBOX PROTEIN 2B (PAIRED-LIKE HOMEOBOX 2B) (PHOX2B HOMEODOMAIN PROTEIN) (NEUROBLASTOMA PHOX) (NBPHOX). 13124 POU6F1: (POU6F1 ORMPOU OR BRNS OR Q14863 Q15944 NM OO2702 TCFB1) POU DOMAIN, CLASS 6, TRANSCRIPTION FACTOR1 (MPOU HOMEOBOX PROTEIN) (BRAIN-SPECIFIC HOMEOBOX/POU DOMAIN PROTEIN 5) (BRN-5 PROTEIN). 13163 SYP: (SYP) SYNAPTOPHYSIN (MAJOR NM OO3179 SYNAPTIC VESICLE PROTEIN P38). US 2008/O 159999 A1 Jul. 3, 2008

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 13219 AHNAK: (AHNAK ORPM227) Q09666 NM OO1620 O.99.12% NEUROBLAST DIFFERENTIATION ASSOCIATED PROTEINAHNAK (DESMOYOKIN) (FLJ33834). 13234 BDNF: ( BDNF) BRAIN-DERIVED NM OO1709 NEURO TROPHICFACTOR PRECURSOR NM 170731 (BDNF). NM 170732 NM 170733 NM 170734 NM 170735 13246 CACNA A: (CACNA1 AOR CACNL1A4 OR P78511 OOO555 NM OOOO68 CACH4 ORCACN3) VOLTAGE-DEPENDENT Q92690 Q16290 NM O23035 P/Q-TYPE CALCIUM CH ANNEL. ALPHA-1A Q99790 Q99791 SUBUN T (CALCIUM CHANNEL, LTYPE, Q99792 Q99793 ALPHA-1 POLYPEPTIDE ISOFORM4) P78510 (BRAIN CALCIUM CHANNEL I) (BI). 13249 CACNA B: (CACNA1B OR CACNL1A5 OR Q00975 NM 000718 CACH5) VO LTAGE-DEPEND ENTN-TYPE CALCIUM CHANNELA LPHA-1B SUBUNIT (CALCIUM CHANNEL, LTYPE, ALPHA-1 POLYPEPTIDE ISOFORM 5) (BRAIN CALCIUM CHANNE L III) (B II). 13252 CACNA1E: (CACNA1E OR CACNL1A6 OR Q15878 Q14581 NM 000721 CACH6) VOLTAGE DEPEND ENTR-TYPE Q14580 CALCIUM CHANNELA LPHA-1E SUBUNIT (CALCIUM CHANN EL, LTYPE, ALPHA-1 POLYPEPTIDE, ISO FORM 6) (BRAIN CALCIUM CHANNE L II) (BI ). 13258 CDC42 1: (CDC42) G2SK GTP-BINDING NM OO1791 1.28.3% PROTEIN, PLACENTCAL SOFORM (GP) (CDC42 HOMOLOG) 13303 GABBR1: (GABBR1) GAMMA NM OO1470 O.93.5% AMINOBUTYRICACID TYP E B RECEPTOR, NM O21903 SUBUNIT 1 PRECU RSOR (GABA-B NM 021904 RECEPTOR ) (GABA-B-R1) (GB1). NM O21905

13309 GABRA1: (GABRA1) GAMMA NM 000806 AMINOBUTYR C-ACID RECEPTOR ALPHA S UBUNIT PRECURSOR (GABA(A) ECEPTOR). 13312 RA2: (GABRA2) GAMMA P47869 NM 000807 INOBUTYRIC-ACID RECEPTOR ALPHA BUNIT PRECURSOR (GABA(A) EPTOR). 13327 : (GABRB3) GAMMA NM 000814 INOBUTYRIC-ACID RECEPTOR BETA-3 NM O21912 UNIT PRECURS O R (GABA(A) EPTOR). 13354 INA: (INA) ALPHA-INTERNEXIN (ALPHA Q16352 NM 032727 INX) (NEUROFILAMENT(-66) (NF-66). Q9BRC5 13402 D: (CACNA1D OR CACNL1A2 OR Q13916 Q13931 NM 000720 CC HL1A2 OR CACH 3 ORCACN4) Q01668 VOLTAGE-DEPENDENT L-TYPE CALCIUM LALPHA DSUBUNIT (CALCIUM ANN L., LTYPE, ALPHA-1 OLYPE TIDE, ISOFORM2). 13411 ACNB1: (CACNB1 ORCACNLB1) Q02641 Q02639 NM 000723 HYDROPYRIDINE-SENSITIVE L-TYPE, Q02640 Q9C085 NM 1992.47 HANN EL BETA-1-B2 SUBUNIT (BETA-1 O15331 NM 199248 OFORMA). 13486 EFH: (NEFHORNF H) NEUROFILAMENT NM 021076 1.65 % RIPLETH PROTEIN (200 KDA EUROFILAMENT PROTEIN) (NEUROFILAMENT HEAVY POLYPEPTIDE) (NF-H). 13489 EFL: (NEFL OR NFL OR NF68) NM OO6158 EUROFILAMENT TRIPLET L PROTEIN (68 DANEUROFILAM ENT PROTEIN) (NEUROFILAMENT LIGHT POLYPEPTIDE) (NF-L). 13492 EF3: (NEF3 OR NE FMORNFM) PO71.97 NM OO5382 EUROFILAMENT TRIPLET MPROTEIN US 2008/O 159999 A1 Jul. 3, 2008 51

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (160 KDANEUROFILAMENT PROTEIN) (NEUROFILAMENT MEDIUM POLYPEPTIDE) (NF-M) (NEUROFILAMENT 3). 13516 NRP2 1: (NRP2 ORVEGF165R2) NM OO3872 O.72.1% NEUROPILIN-2 PRECURSOR (VASCULAR NM 018534 ENDOTHELLAL CELL GROWTH FACTOR NM 201266 165 RECEPTOR2). NM 201267 NM 201279 13543 POU3F2: (POU3F2 OR BRN2 OR OTF7 OR NM OO5604 OCT7) NERVOUS-SYSTEM SPECIFIC OCTAMER-BINDING TRANSCRIPTION FACTORN-OCT3 (BRAIN-SPECIFIC HOMEOBOX/POU DOMAIN PROTEIN 2) (BRN-2 PROTEIN). 13582 SMDF: (NRG1 OR HGL OR NDF OR HRGA Q15491 NM O13959 O.79, 96 ORGGF OR SMDF) NEUREGULIN-1, SENSORY AND MOTOR NEURON-DERIVED FACTOR ISOFORM. 13591 STX1A: (STX1A OR STX1) SYNTAXIN 1A O15448 NM 004603 1.2112% (NEURON-SPECIFIC ANTIGEN HPC-1). Q9BPZ6 Q12936 O15447 Q16623 13597 SYN2: (SYN2) SYNAPSIN II. Q92777 NM OO3178 NM 133625 14615 CLCN3: (CLCN3) CHLORIDE CHANNEL NM OO1829 PROTEIN3 (CLC-3) (CLC-3) 14618 CLCN7: (CLCN7) CHLORIDE CHANNEL NM 001287 PROTEIN 7 (CLC-7). 14716 COL9A1 2: (COL9A1) COLLAGEN ALPHA NMOO1851 1.31.22% 1(IX) CHAIN PRECURSOR.

14734 PRKCB 3: (PRKCB1 OR PRKCB OR PKCB) NM 212535 PROTEIN KINASEC, BETA TYPE (EC 2.7.1.37) (PKC-BETA) (PKC-B).

14740 PPARG 2: (PPARG ORNR1C3) NM O15869 PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPAR GAMMA) (PPARG2). 14746 PRKCA: (PRKCA OR PKCA) PROTEIN NM OO2737 KINASEC, ALPHATYPE (EC 2.7.1. ) (PKC ALPHA). 14749 VEGFA: (VEGF ORVEGFA) VASCULAR NM 001025366 O.33.25% ENDOTHELLAL GROWTH FACTOR NM 00102.5367 PRECURSOR (VEGF-A) (VASCULAR NM 001025368 PERMEABILITY FACTOR) (VPF). NM 001025369 NM 001025370

14752 VGR1: (FLT1 ORFLT OR FRT) VASCULAR NM OO2019 O.O1,108% ENDOTHELLAL GROWTH FACTOR RECEPTOR 1 PRECURSOR (EC 2.7.1.112) (VEGFR-1) (TYROSINE-PROTEIN KINASE RECEPTOR FLT) (FLT-1) (TYROSINE ROTEIN KINASE FRT). 14773 KT2: (AKT2) RAC-BETA P31751 Q68GCO NM OO1626 E RINETHREONINE PROTEIN KINASE (EC 7 1. ) (RAC-PK-BETA) (PROTEIN KINASE KT-2) (PROTEIN KINASEB, BETA) (PKB ETA). 14776 KT3: (AKT3) RAC-GAMMA NM OO5465 E RINETHREONINE PROTEIN KINASE (EC 7 .1. ) (RAC-PK-GAMMA) (PROTEIN (NASEAKT-3) (PROTEIN KINASEB, GAMMA) (PKB GAMMA). US 2008/O 159999 A1 Jul. 3, 2008 52

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 14809 BUB1: (BUB1 OR BUB1L) MITOTIC O60626 O43643 NM 004336 CHECKPOINT SERINETHREONINE O43430 O43683 PROTEIN KINASE BUB1 (EC 2.7.1. ) (HBUB1) (BUB1A). 15028 MAPK13: (MAPK13 OR PRKM13 ORSAPK4) O14739 O15124 NM O02754 MITOGEN-ACTIVATED PROTEINKINASE Q9UNUO 3 EC O15264

( 2.7.1.- ) (STRESS-ACTIVATED R IN KINASE-4) (MITOGEN O (VATED PROTEIN KINASE P38 DELTA) sMAP KINASE P38 DELTA). 5092 A1: (EPHA1 OR EPHT1 OR EPHT OR Q15405 P21709 NM OO5232 ) EPHRIN TYPE-A RECEPTOR 1 CURSOR (EC 2.7.1.112) (TYROSINE OTEIN KINASE RECEPTOR EPH). S101 C A4: (EPHA4 OR SEK OR HEK8) EPHRIN PS4764 NM 004438 TYp A RECEPTOR4 PRECURSOR (EC 2. 7 12) (TYROSINE-PROTEIN KINASE R E PTORSEK) (RECEPTOR PROTEIN s SINE KINASE HEK8). S116 E 4: (EPHB4 OR HTK) EPHRIN TYPE-B NM OO4444 1.31.26% s PTOR4 PRECURSOR (EC 2.7.1.112) (TYROSINE-PROTEIN KINASE RECEPTOR HTK). S194 PAK1: (PAK1) SERINE THREONINE NM OO2576 PROTEIN KINASE PAK 1 (EC 2.7.1.- ) (P21 ACTIVATED KINASE 1) (PAK-1) (P65-PAK) (ALPHA-PAK). 5296 TEK: (TEKORTIE2) ANGIOPOIETIN 1 NM 000459 RECEPTOR PRECURSOR (EC 2.7.1.112) (TYROSINE-PROTEIN KINASE RECEPTOR TIE-2) (TYROSINE-PROTEIN KINASE RECEPTOR TEK) (P140 TEK) (TUNICA INTERNA ENDOTHELIAL CELL, KINASE) (CD202B ANTIGEN). 15308 TIE1: (TIE1 OR TIE) TYROSINE-PROTEIN P35590 NM 005424 KINASE RECEPTOR TIE-1 PRECURSOR (EC 2.7.1.112). 15492 MAP3K3: (MAP3K3 ORMAPKKK3 OR Q997.59 NM OO2401 MEKK3) MITOGEN-ACTIVATED PROTEIN NM 203351 KINASE KINASE KINASE 3 (EC 2.7.1. ) (MAPK/ERK KINASE KINASE 3) (MEK KINASE 3) (MEKK3). 15495 MAP3K4: (MAP3K4 OR MAPKKK4 OR NM OO5922 0.93.77% EKK4 ORMTK1 OR KIAA0213) MITOGEN NM OO6724 CTIVATED PROTEINKINASEKINASE (NASE 4 (EC 2.7.1. ) (MAPK/ERK KINASE (NASE 4) (MEK KINASE 4) (MEKK4) (MAP HREE KINASE 1). 15609 RKCN; (PRKCN OR EPK2) PROTEIN O94806 NM OO5813 KINASEC, NUTYPE (EC 2.7.1. ) (NPKC-NU) (PROTEIN KINASE EPK2). 15723 CSX: (NKX2E ORCSXOR NKX2-5) P52952 NM 004387 HOMEOBOX PROTEIN NKX-2.5 (CARDIAC SPECIFIC HOMEOBOX) (HOMEOBOX PROTEIN CSX). 15741 TGIF2: (TGIF2) HOMEOBOX PROTEIN NM O21809 TGIF2 (TGFB-INDUCED FACTOR2) (5'-TG-3' INTERACTING FACTOR2) (TGF(BETA)- INDUCED TRANSCRIPTION FACTOR2) (DJ977B14). 15750 DLX2: (DLX2) HOMEOBOX PROTEINDLX Q07687 NM OO4405 2. 15762 DLX5: (DLX5) HOMEOBOX PROTEINDLX-5 Q9UPL1 P56178 NM OO5221 (DLX-5 BETA). 15783 EN1: (EN1) HOMEOBOX PROTEIN Q05925 NM OO1426 ENGRAILED-1 (HU-EN-1). 15852 HOXB3: (HOXB3 OR HOX2G) HOMEOBOX P17484 O9.5615 NM 002146 PROTEIN HOX-B3 (HOX-2G) (HOX-2.7). P14651 15906 PITX2: (PITX2 ORRIEG1 ORRIEGORRGS NM OOO325 O.62.23% OR ARP1) PITUITARY HOMEOBOX 2 (RIEG NM 153426 US 2008/O 159999 A1 Jul. 3, 2008 53

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 BICOID-RELATED HOMEOBOX O60580 Q99697 NM 153427 TRANSCRIPTION FACTOR) (SOLURSHIN) (ALL1 RESPONSIVE PROTEIN ARP1). 15915 POU2F2: (POU2F2 OR OTF2 OR OCT2) PO9086 Q9BRS4 NM 002698 OCTAMER-BINDING TRANSCRIPTION Q16648 FACTOR2 (OTF-2) (LYMPHOID RESTRICTED IMMUNOGLOBULIN OCTAMERBINDING PROTEIN NF-A2) (OCT-2 FACTOR). 15918 POUSF 1: (POUSF1 OR OTF3 OROCT3 OR NM OO2701 1.48 42% OCT4) OCTAMER-BINDING TRANSCRIPTION FACTOR3A (OCT-3A) (OCT-4) (POUSFLC20) (POU5 DOMAIN PROTEIN) (POUSFLC8) (OTF3C) (OCTAMER-BINDING TRANSCRIPTION FACTOR3C) (OCT-3C) (POUSFLC1) (POUSFLC12). 5945 TCF2 1: (TCF2 OR HNF1B) HEPATOCYTE P3568O NM 000458 NUCLEAR FACTOR1-BETA (HNF-1B) (VARLANT HEPATIC NUCLEAR FACTOR 1) (VHNF1) (HOMEOPROTEIN LFB3) (TRANSCRIPTION FACTOR2) (TCF-2). 5999 HOXB2: (HOXB2 OR HOX2H) HOMEOBOX P17485 P10913 NM 002145 PROTEIN HOX-B2 (HOX-2H) (HOX-2.8) (K8). P14652 Q14548 HOXD3: (HOXD3 OR HOX4A) HOMEOBOX Q9BSC5 NM O06898 1.02 % PROTEIN HOX-D3 (HOX-4A). Q99955 P31249 ISL1: (ISL1) INSULINGENE ENHANCER P47894 P20663 NM OO2202 1.30.6% PROTEIN ISL-1 (ISLET-1). P61371 6089 LHX2: (LHX2 OR LH2) LIM/HOMEOBOX O95860 PSO458 NM 004789 1.10.23% PROTEIN LHX2 (HOMEOBOX PROTEIN LH Q8N1Z3 2). 6116 NKX2-2: (NKX2-2 OR NKX2B OR NKX2.2) O95096 NM OO2509 HOMEOBOX PROTEIN NKX-22 (HOMEOBOX PROTEIN NK-2 HOMOLOGB). 61.38 OTX2: (OTX2) HOMEOBOX PROTEIN OTX2. NM 021728 NM 172337

6140 PAX6: (PAX6 ORAN2) PAIRED BOX NM OO1604 PROTEIN PAX-6 (OCULORHOMBIN) (ANIRIDIA, TYPE II PROTEIN). 6143 PAX7: (PAX7 OR HUP1) PAIRED BOX P23759 NM OO2584 PROTEIN PAX-7 (HUP1). NM O13945 6534 AIF 1: (AIF1 ORIBA1) ALLOGRAFT P55008 NM OO1623 1.09 % INFLAMMATORY FACTOR-1 (AIF-1) Q9UKS9 NM OO4847 (IONIZED CALCIUM-BINDING ADAPTER NM 032955 MOLECULE 1). 6555 CALU: (CALU) CALUMENIN PRECURSOR. NM OO1219 0.46.8%

6663 MYL2: (MYL2) MYOSIN REGULATORY NM 000432 LIGHT CHAIN 2, VENTRICULAR/CARDIAC MUSCLE ISOFORM (MLC-2). 6666 MYL7: (MYL7 OR MYLC2A) MYOSIN Q01449 NM 021223 1.61f46% MYOSIN REGULATORY LIGHT CHAIN 2, ATRIAL ISOFORM (MYOSIN LIGHT CHAIN 2A) (MLC-2A) (MLC2A) (MYOSIN REGULATORY LIGHT CHAIN 7) (MYL2 Q01449). 16675 MYL4: (MYLA ORMLC1) MYOSIN LIGHT P11783 P12829 NM OO2476 CHAIN 1, EMBRYONIC MUSCLEATRIAL ISOFORM (PRO1957). MYOSIN LIGHT CHAINALKALI, GT-1 ISOFORM (FRAGMENT). 16826 ANKRD17 1: (4933425K22RIK OR GTAR) NM O32217 GENE TRAPANKYRIN REPEAT CONTAINING PROTEIN (KIAA0697) (ANKYRIN REPEAT DOMAIN 17) (ANKRD17) (SEROLOGICALLY DEFINED BREAST CANCERANTIGEN NY-BR-16) (FLJ22206) (DKFZP547D039). US 2008/O 159999 A1 Jul. 3, 2008 54

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 16888 RTN4: (RTN4 OR NOGO ORASYOR NM OO7008 KIAAO886) RETICULON 4 (NEURITE NM 020532 OUTGROWTH INHIBITOR) (NOGO NM 153828 PROTEIN) (FOOCEN) (NEUROENDOCRINE NM 2075.20 SPECIFIC PROTEIN) (NSP) NM 207521 (NEUROENDOCRINE SPECIFIC PROTEINC HOMOLOG) (RTN-X) (RETICULON5) (MY043 PROTEIN). 6891 S100A10: (S100A10 OR CAL1 LORANX2LG NM OO2966 O.89.6% ORCLP11) CALPACTINI LIGHT CHAIN (P10 PROTEIN) (P11) (CELLULAR LIGAND OF ANNEXIN II). 6897 SEMA3C: (SEMA3C OR SEMAE) Q99985 NM OO6379 107.12% SEMAPHORIN3C PRECURSOR (SEMAPHORINE) (SEMAE). 6903 SET: (SET) SET PROTEIN (HLA-DR NM OO3011 0.68, -96 ASSOCIATED PROTEIN II) (PHAPII) (PHOSPHATASE 2A INHIBITORI2PP2A). 6924 SOX15: (SOX15 OR SOX12 OR SOX20 OR NM OO6942 SOX26 OR SOX27) SOX-15 PROTEIN (SOX 20 PROTEIN) (SOX-12 PROTEIN). 7113 GJB3: (GJB3 ORCX31) GAP JUNCTION O75712 NM 024009 BETA-3 PROTEIN (CONNEXIN 31) (CX31). 71.61 IGHA1-IGHA2 HUMAN: (IGHA1) IGALPHA PO1876 PO1877 1 CHAINCREGION (IGHA2) IGALPHA-2 CHAINCREGION. 7641 TNNC1: (TNNC1 ORTNNC) TROPONINC, P63316 NM OO3280 1.31.10% SLOWSKELETAL AND CARDIAC MUSCLES (TN-C). 7674 SERPINA1 2 HUMAN: (SERPINA1 ORPIOR NM 000295 1.09 % AAT) ALPHA-1-ANTITRYPSIN PRECURSOR (ALPHA-1 PROTEASE INHIBITOR) (ALPHA 1-ANTIPROTEINASE). 7843 DLK1: (DLK1 OR DLKOR PREF1 ORSCP-1) NM OO3836 DELTA-LIKE PROTEIN PRECURSOR (DLK) (PREADIPOCYTE FACTOR 1) (PREF-1) (ADIPOCYTE DIFFERENTIATION INHIBITOR PROTEIN). (ZOG)ZOG. 17848 DNMT1: (DNMT1 OR DNMT ORAIM) DNA NM 001379 (CYTOSINE-5)-METHYLTRANSFERASE HSAI (EC 2.1.1.37) (DNA METHYLTRANSFERASE HSAI) (DNA MTASE HSAI) (MCMT) (M.HSAI). 17851 DNMT2: (DNMT2) MODIFICATION O43669 O14717 NM 004412 1.63.28% METHYLASE (EC 2.1.1.73) (CYTOSINE NM 76081 SPECIFIC METHYLTRANSFERASE). NM 76083 NM 76084 176085 176086 17854 DNMT3A 1: (DNMT3A) MODIFICATION METHYLASE (EC 2.1.1.73) (CYTOSINE SPECIFIC METHYLTRANSFERASE). 17857 DNMT3B: (DJ1085F17.1 OR DNMT3B) MODIFICATION METHYLASE ISOFORM1 (EC 2.1.1.73) (CYTOSINE-SPECIFIC METHYLTRANSFERASE).

17860 DNMT3L: (DNMT3L) CYTOSINE-5- METHYLTRANSFERASE3-LIKE PROTEIN. 17864 EFNB1: (EFNB1 OR EPLG2 OR LERK2 OR NM 004.429 STRA1 OR EPL2) EPHRIN-B1 PRECURSOR (EPH-RELATED RECEPTORTYROSINE KINASE LIGAND 2) (LERK-2) (ELK LIGAND) (ELK-L) (STRA1 PROTEIN) (CEK5 RECEPTOR LIGAND) (CEK5-L) (EFL2). 17920 HDC: (HDC) HISTIDINE DECARBOXYLASE P19113 NM 002112 (EC 4.1.1.22) (HDC). 17935 IFNGR2: (IFNGR2 ORIFNGT1) NM 005534 O67.5% INTERFERON-GAMMA RECEPTOR BETA CHAIN PRECURSOR(INTERFERON US 2008/O 159999 A1 Jul. 3, 2008 55

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 GAMMA RECEPTOR ACCESSORY FACTOR 1) (AF-1) (INTERFERON-GAMMA TRANSDUCER-1). 17954 KCNQ1: (KCNQ1 OR KCNA9 OR KVLQT1) NM 000218 1.52.22% VOLTAGE-GATED POTASSIUM CHANNEL NM 181797 PROTEIN KQT-LIKE 1 (KVLQT1) (KV1.9). NM 181798

17969 MAP1B: (MAP1B ORMTAP5) NM OO5909 0.90 % MICROTUBULE-ASSOCIATED PROTEIN 1B NM 032010 (MAP1.2) (MAP1(X)). 17987 NES: (NES) INTERMEDIATE FILAMENT OOOSS2P48681 NM OO6617 PROTEINNESTIN. 18017 PTCH2: (PTCH2) PATCHED PROTEIN NM 003738 HOMOLOG 2 (PTC2).

1802O RAMP2: (RAMP2) RECEPTORACTIVITY NM OO5854 MODIFYING PROTEIN 2 PRECURSOR (CRLRACTIVITY-MODIFYING-PROTEIN 2) (CALCITONIN-RECEPTOR-LIKE RECEPTOR-ACTIVITY MODIFYING PROTEIN 2). 1816O HDAC2: (HDAC2) HISTONE DEACETYLASE NM OO1527 1.14.8% 2 (HD2). 18164 HMGIY: (HMGIY OR HMGA1 OR HMGI) NM 002131 1.56.17% HIGHMOBILITY GROUP PROTEIN HMG-Y NM 145899 (HIGH MOBILITY GROUP AT-HOOK 1). NM 145901 NM 145902 NM 145903 NM 145904 NM 1 18167 HRAS: (HRAS1 OR HRAS) GTPASE HRAS NM OO5343 1.31f41% PRECURSOR (TRANSFORMING PROTEIN NM 176795 P21) (H-RAS-1) (C-H-RAS). 18358 ESM1: (ESM1) ENDOTHELIAL CELL NM 007036 SPECIFIC MOLECULE 1 PRECURSOR (ESM 1 SECRETORY PROTEIN) (ESM-1). 18379 UBE2T: (UBE2T OR HSPC150) UBIQUITIN NM 014176 CONJUGATING ENZYME E2T (EC 6.3.2.19) (UBIQUITIN-PROTEIN LIGASET) (UBIQUITIN CARRIER PROTEINT) (FLJ20497) (2700084L22RIK). 1838S IGFBP2: (IGFBP2 OR BP2) INSULIN-LIKE NM 000597 GROWTH FACTORBINDING PROTEIN 2 PRECURSOR(IGFBP-2) (IBP-2) (IGF BINDING PROTEIN 2). 18388 IGFBP5: (IGFBP5 OR IBP5) INSULIN-LIKE P24593 NM 000599 GROWTH FACTORBINDING PROTEINS QSUOA3 PRECURSOR(IGFBP-5) (IBP-5) (IGF BINDING PROTEIN5). 19048 ALB: (ALBORALB1 OR ALB-1) SERUM NM 000477 ALBUMIN PRECURSOR

19408 RNF138: (RNF138) RING FINGER PROTEIN NM O16271 138 (STRIN) (TRIF) (RSD-4) (FLJ13517) (HSD NM 1981.28 4) (DKFZP434I1714) (2410015A17RIK). 19669 EPRS: (EPRS OR QPRS OR GLNS OR PARS) NM 004446 BIFUNCTIONALAMINOACYL-TRNA SYNTHETASE INCLUDES: GLUTAMYL TRNASYNTHETASE (EC 6.1.1.17) (GLUTAMATE-TRNA LIGASE); PROLYL TRNASYNTHETASE (EC 6.1.1.15) (PROLINE-TRNA LIGASE)). 19690 RPLPO: (RPLPO) 60S ACIDICRIBOSOMAL NM OO10O2 1.08.3% PROTEIN PO (L10E). NM 053275 US 2008/O 159999 A1 Jul. 3, 2008 56

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 19759 F7: (F7) COAGULATION FACTOR VII P08709 Q14339 NM 000131 PRECURSOR (EC 3.4.21.21) (SERUM Q5JVF2 NM 019616 PROTHROMBIN CONVERSION ACCELERATOR) (EPTACOGALFA). 19919 SMURF1: (SMURF1 OR KIAA1625) SMAD Q9UJT8 NM 020429 UBIQUITINATION REGULATORY FACTOR Q9HCE7 NM 181349 (EC 6.3.2. ) (UBIQUITIN--PROTEIN LIGASE O75853 SMURF1) (SMAD-SPECIFIC E3 UBIQUITIN LIGASE 1) (HSMURF1) (4930431E1ORIK). 19922 SMURF2: (SMURF2) SMAD Q9HAU4 NM O22739 UBIQUITINATION REGULATORY FACTOR Q9H260 2 (EC 6.3.2. ) (UBIQUITIN--PROTEIN LIGASE SMURF2) (SMAD-SPECIFIC E3 UBIQUITIN LIGASE 2) (HSMURF2) (2810411 E22RIK). 20039 GATA6: (GATA6) TRANSCRIPTION Q92908 P78327 NM OO5257 FACTOR GATA-6 (GATA BINDING FACTOR-6)(DNA BINDINGPROTEIN GATA GT2). 20324 ADAM15: (ADAM15 OR MDC15) ADAM 15 Q13444 Q13493 NM OO3815 O.90.8% PRECURSOR (EC 3.4.24- ) (A DISINTEGRIN Q96C78 NM 207191 AND METALLOPROTEINASE DOMAIN 15) NM 207194 (METALLOPROTEINASE-LIKE, NM 207195 DISINTEGRIN-LIKE, AND CYSTEINE-RICH NM 207196 PROTEIN 15) (MDC-15) NM 2071.97 (METALLOPROTEASE RGD DISINTEGRIN PROTEIN) (METARGIDIN) (AD56) (CRII 20511 PLXNA3: (PLXNA3 OR PLXN4 OR SEX) P51805 NM 017514 PLEXIN A3 PRECURSOR (PLEXIN 4) QSHY36 (TRANSMEMBRANE PROTEINSEX) (PLXN3) (PLEXIN3). 20526 SEM2: (SEM2) SEMAPHORINSEM2. Q9NS98 Q9H7O3 Q7L9D9 20529 SEMA3A: (SEMA3A) SEMAPHORIN3A Q14563 NM OO6080 PRECURSOR (SEMAPHORIN III) (SEMA III). (SEMA3A OR SEMAD OR SEMD) SEMAPHORIN3APRECURSOR (SEMAPHORIN III) (SEMA III) (SEMAPHORIN D) (SEMAD). 20532 SEMA3B: (SEMA3B OR SEMAS) Q13214 Q93018 NM 004636 SEMAPHORIN3B PRECURSOR Q8TDV7 (SEMAPHORINV) (SEMAV). (SEMA3B OR Q8TB71 SEMAA OR SEMA) SEMAPHORIN3B Q96GXO PRECURSOR (SEMAPHORINA) (SEMAA). 20538 SEMA3E: (SEMA3E OR KIAA0331) O15041 NM 012431 SEMAPHORIN3E PRECURSOR. (SEMA3E Q75M94 ORSEMAHORSEMH) SEMAPHORIN3E Q75M97 PRECURSOR (SEMAPHORIN H) (SEMA H). 20541 SEMA3F: (SEMA3F) SEMAPHORIN3F Q13275 Q15704 NM 004186 PRECURSOR (SEMAPHORIN IV) (SEMA IV) Q13372 Q13274 (SEMA III/F). 20547 SEMA4F: (SEMA4F OR SEMAW OR SEMAM) O95754 NM 004263 SEMAPHORIN 4F PRECURSOR Q9NS35 (SEMAPHORINW) (SEMAW). 20559 SEMA6A1: (SEMA6A1) SEMAPHORIN Q9H2E6 SEMA6A1. (SEMA6A OR SEMAQ) Q9P2H9 SEMAPHORIN 6A PRECURSOR (SEMAPHORIN VIA) (SEMA VIA) (SEMAPHORINQ) (SEMAQ). 20586 SEMA4C: (SEMA4C OR KIAA1739) Q9COC4 NM O17789 SEMAPHORIN4C PRECURSOR (SEMAI) Q7Z5XO (SEMACL1) (SEMAPHORINC-LIKE 1) (UNQ5855/PRO34487). 20616 ASPIC1: (ASPIC1 ORCEP-68) ASPIC Q9NQ79 NM 018058 PRECURSOR (CHONDROCYTE EXPRESSED Q9NQ80 PROTEIN 68 KDA) ((2810454P21RIKOR Q9NQ78 CRTAC1) (CRTAC1-B PROTEIN) Q8TE52 (CARTILAGE ACIDIC PROTEIN 1) Q8N4H6 (FLJ10320). Q9NW46 20646 PIK3C2B: (PIK3C2B) OOO7SO O95666 NM 002646 PHOSPHATIDYLINOSITOL 3-KINASEC2 Q5SW99 DOMAIN-CONTAINING BETA POLYPEPTIDE (EC 2.7.1.137) US 2008/O 159999 A1 Jul. 3, 2008 57

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 (PHOSPHOINOSITIDE 3-KINASE-C2-BETA) (PTDINS-3-KINASEC2 BETA) (PI3K C2BETA) (C2-PI3K). 21270 SCARB2: (SCARB2 ORCD36L2 OR LIMPII) Q14108 NM OO5506 0.64-96 LYSOSOME MEMBRANE PROTEIN II (LIMP II) (85 KDALYSOSOMAL MEMBRANE SIALOGLYCOPROTEIN) (LGP85) (CD36 ANTIGEN-LIKE2). 21478 VIM: (VIM) VIMENTIN. NM OO3380 O.80.10%

21481 VTN: (VTN) VITRONECTIN PRECURSOR NM 000638 (SERUMSPREADING FACTOR) (S- PROTEIN). 21778 CDC42 2: (CDC42B ORCDC42) G25K GTP NM 044472 BINDING PROTEIN, BRAIN ISOFORM (GP) (CDC42 HOMOLOG). 21835 KRAS 1: (KRAS OR KRAS2 OR RASK2) PO1118 PO1116 NM OO4985 O.S1.27% GTPASE KRAS (K-RAS 2) (KI-RAS) (C-K- Q96D10 NM 03.3360 RAS). 22O15 TC10-PIGF: (RHOQ OR ARHQ OR TC10) NM 002643 O.99.2% RHO-RELATED GTP-BINDING PROTEIN NM 012249 RHOQ (RAS-RELATED GTP-BINDING NM 173074 PROTEIN TC10) (RHO-LIKE GTP-BINDING PROTEIN TC10) (PIGF) PHOSPHATIDYLINOSITOL-GLYCAN B OSYNTHESIS, CLASS F PROTEIN) (PIG-F). 22039 CSN1 3PRIME: (CSN1 OR GPS1 OR COPS1) NM 004127 1.16.10% COP9 SIGNALOSOME COMPLEX SUBUNIT NM 212492 (SIGNALOSOME SUBUNIT 1) (SGN1) (JAB1-CONTAINING SIGNALOSOME SUBUNIT 1) (GPROTEIN PATHWAY SUPPRESSOR1) (GPS1 PROTEIN) (MF PROTEIN) (GPS1 3PRIME). 22114 HBZ: (HBZ OR HBZ2) HEMOGLOBIN ZETA PO2008 NM 005332 CHAIN. 22441 GAL: (GAL OR GAL1 OR GALN OR GLNN) P22466 Q14413 NM O15973 GALANIN PRECURSOR 224.53 CNQ3: (KCNQ3) VOLTAGE-GATED NM OO4519 POTASSIUM CHANNEL PROTEIN KQT LIKE 3. 22462 RAMP1: (RAMP1) RECEPTORACTIVITY O60894 NM OO5855 MODIFYING PROTEIN 1. 2246S RAMP3: (RAMP3) RECEPTORACTIVITY O60896 NM OO5856 MODIFYING PROTEIN3. 22584 GNL3: (GNL3 ORE2IG3 ORNS). GUANINE NM O14366 NUCLEOTIDE BINDING PROTEIN-LIKE 3 NM 206825 (NUCLEOLAR GTP-BINDING PROTEIN3) NM 206826 (NUCLEOSTEMIN) (E2-INDUCED GENE 3 PROTEIN) (NOVEL NUCLEOLAR PROTEIN 47) (NNP47) (FLJ14610) (FLJ14608) (C77032). 22644 GBP2: (GBP2) INTERFERON-INDUCED P32456 Q86TBO NM 004120 GUANYLATE-BINDING PROTEIN 2 (GUANINE NUCLEOTIDE-BINDING PROTEIN 2) (MGBP-2). 22663 HNRPA1: (HNRPA1) HETEROGENEOUS NM 002136 NUCLEARRIBONUCLEOPROTEIN A1 NM 031157 (HELIX-DESTABILIZING PROTEIN) (SINGLE-STRAND BINDING PROTEIN) (HNRNP CORE PROTEIN A1). 22693 MYH7: (MYH7 OR MYHCB) MYOSIN NM OOO257 HEAVY CHAIN, CARDIAC MUSCLE BETA ISOFORM (MYHC-BETA).

22699 NASP 1: (NASP) NUCLEAR NM OO2482 AUTOANTIGENICSPERM PROTEIN (NASP). NM 172164 US 2008/O 159999 A1 Jul. 3, 2008 58

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 RPL6: (RPL6) 60S RIBOSOMAL PROTEIN L6 NM OOO970 1.23.17% (TAX-RESPONSIVE ENHANCERELEMENT BINDING PROTEIN 107) (TAXREB107) (NEOPLASM-RELATED PROTEIN C140). 22935 DDX21: (DDX21) NUCLEOLAR RNA NM OO4728 HELICASE II (NUCLEOLAR RNA HELICASE GU) (RH II/GU) (DEAD BOX PROTEIN 21). 23209 KCNJ11: (KCNJ11) ATP-SENSITIVE NM 000525 NWARD RECTIFIERPOTASSIUM CHANNEL 11 (POTASSIUM CHANNEL, NWARDLY RECTIFYING, SUBFAMILY J, MEMBER 11) (INWARD RECTIFIERK+ CHANNEL KIR6.2) (IKATP). 23212 KCNJ3: (KCNJ3 ORGIRK1) GPROTEIN NM OO2239 ACTIVATED INWARD RECTIFIER POTASSIUM CHANNEL 1 (GIRK1) (POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER3) (INWARD RECTIFIERK+ CHANNEL KIR3.1). 23215 KCNJ6: (KCNJ6 OR KCNJ7 ORGIRK2OR NM 002240 KATP2) GPROTEIN-ACTIVATED INWARD RECTIFIERPOTASSIUM CHANNEL 2 (GIRK2) (POTASSIUM CHANNEL, NWARDLY RECTIFYING, SUBFAMILY J, MEMBER 6) (INWARD RECTIFIER K+ CHANNEL KIR3.2) (KATP-2) (BIR1). 23218 KCNJ9: (KCNJ9 ORGIRK3) GPROTEIN NM OO4983 ACTIVATED INWARD RECTIFIER POTASSIUM CHANNEL 3 (GIRK3) (POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 9) (INWARDLY RECTIFIER K+ CHANNEL KIR3.3). 23248 SOX2: (SOX2) TRANSCRIPTION FACTOR P48431 Q14537 NM OO3106 SOX-2. 23322 LDN1: (CLDN1 OR CLD1 OR SEMP1) O95832 NM 021101 O.71.20% LAUDIN-1 (SENESCENCE-ASSOCIATED ITHELLAL MEMBRANE PROTEIN). 23325 LDN10: (CLDN10) CLAUDIN-10 (OSP LIKE P78369 NM OO6984 OTEIN). NM 182848 23361 LDN4: (CLDN4 ORCPETR1 ORCPEROR O14493 NM OO1305 O.11.10% WBSCR8) CLAUDIN-4 (CLOSTRIDIUM PERFRINGENS ENTEROTOXIN RECEPTOR) (CPE-RECEPTOR) (CPE-R). 23364 LDN5: (CLDNS ORTMVCF) CLAUDIN-5 NM OO3277 TRANSMEMBRANE PROTEIN DELETED IN CFS) (TMDVCF) 23367 LDN6: (CLDN6) CLAUDIN-6 (SKULLIN 2). NM 021195 O.09.40% 23370 LDN7: (CLDN7) CLAUDIN-7. NM OO1307

23433 C3ORF4: (C3ORF4 ORPSEC0054 OR NM O19895 HSPC174) PROTEIN C3ORF4 (MEMBRANE PROTEINGENX-3745) (CHROMOSOME 3 OPEN READING FRAME 4) (UNQ2511/PRO6000). 23565 GJB4: (GJB4 ORCXN-30.3) GAP JUNCTION NM 153212 BETA-4 PROTEIN (CONNEXIN 303) (CX30.3). 24432 CRDBP: (IGF2BP1 OR CRDBP) MRNA NM OO6546 BINDING PROTEIN CRDBP (CODING REGION DETERMINANT BINDING PROTEIN) (B-ACTINZIPCODE BINDING PROTEIN 1). 24438 ELAVL4: (ELAVL4 OR HUD OR PNEM) NM O21952 ELAV-LIKE PROTEIN 4 (PARANEOPLASTIC ENCEPHALOMYELITIS ANTIGEN HUD) (HU-ANTIGEND). US 2008/O 159999 A1 Jul. 3, 2008 59

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 24570 MSI2 1: (MSI2HORMSI2) RNA-BINDING NM 138962 PROTEIN MUSASHIHOMOLOG 2 (MUSASHI-2) (RNA-BINDING PROTEIN MUSASHI2). 24627 CDH15: (CDH15 ORCDH14 ORCDH3) P55291 NM OO4933 MUSCLE-CADHERIN PRECURSOR (M- CADHERIN) (CADHERIN-15) (CADHERIN 14). 24645 CDH4: (CDH4) CADHERIN-4 PRECURSOR NM OO1794 (RETINAL-CADHERIN) (R-CADHERIN) (R- CAD) (BA489M19.1). 24678 DSG2: (DSG2) DESMOGLEIN 2 PRECURSOR NM OO1943 (HDGC). 24938 C20ORF1: (C20ORF1 ORC20ORF2 OR DIL2 NM 012112 ORTPX2) RESTRICTED EXPRESSION PROLIFERATIONASSOCIATED PROTEIN 100 (P100) (DIFFERENTIALLY EXPRESSED IN LUNG CELLS 2) (DIL-2) (TARGETING PROTEINFORXKLP2) (C20ORF1 PROTEIN) (C20ORF2 PROTEIN) (PROTEIN FLS353). 24947 CLCN6 1: (CLCN6 OR KIAA0046) P51797 P78521 NM 001286 CHLORIDE CHANNEL PROTEIN 6 (CLC-6). O60818 Q99427 Q99428 Q99429 O60819 O60820 O60821 P 24.96S DPYSL3: (DPYSL3 ORULIP ORDRP3 OR Q14195 Q93012 NM OO1387 0.37.25% CRMP4) DIHYDROPYRIMIDINASE RELATED PROTEIN-3 (DRP-3) (UNC-33 LIKE PHOSPHOPROTEIN) (ULIP PROTEIN) (COLLAPSIN RESPONSE MEDIATOR PROTEIN 4) (CRMP-4). 2SO40 PUM2: (PUM2 OR PUMH2ORKIAA0235) NM O15317 PUMILIO HOMOLOG 2 (PUMILIO2) (PUMM2) (PUMILIO 2) (TRANSLATIONAL REPRESSOR PUMILIO). 25052 KITLG: (KITLG ORMGF ORSCF) KIT NM OO3994 LIGAND PRECURSOR(C-KIT LIGAND) (STEM CELL FACTOR) (SCF) (MAST CELL GROWTH FACTOR) (MGF). 25213 HCN1: (HCN1 OR BCNG1 OR HAC2) O60741 NM 021072 POTASSIUMFSODIUM HYPERPOLARIZATION-ACTIVATED CYCLICNUCLEOTIDE-GATED CHANNEL 1 (BRAINCYCLIC NUCLEOTIDE GATED CHANNEL 1) (BCNG-1) (HYPERPOLARIZATION-ACTIVATED CATION CHANNEL 2) (HAC-2). 25.222 CACNA1G 1: (CACNA1G ORKIAA1123) NM 018896 1.02.26% VOLTAGE-DEPENDENTT TYPE CALCIUM NM 198376 CHANNEL ALPHA-1G SUBUNIT (NBR13) NM 198377 (CAV3.1C). NM 198378 NM 198379 NM 198380 NM 1 25225 CACNA1 H: (CACNA1 H) VOLTAGE NM 021098 1.41f4% DEPENDENTT TYPE CALCIUM CHANNEL ALPEHA-1H SUBUNIT.

25279 KCNH5 1: (KCNH5 OR EAG2) POTASSIUM NM 1393.18 VOLTAGE-GATED CHANNEL SUBFAMILY NM 172375 H MEMBER5 (ETHER-A-GO-GO POTASSIUM CHANNEL 2) (HEAG2). 25297 HCN2: (HCN2 OR BCNG2) NM OO1194 HYPERPOLARIZATION-ACTIVATED, CYCLICNUCLEOTIDE-GATED CHANNEL 2 (HAC1). 2S300 HCN4: (HCN4 OR BCNG3) NM 005477 POTASSIUMFSODIUM US 2008/O 159999 A1 Jul. 3, 2008 60

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 HYPERPOLARIZATION-ACTIVATED CYCLICNUCLEOTIDE-GATED CHANNEL 4 (BRAINCYCLIC NUCLEOTIDE GATED CHANNEL3) (BCNG-3). 25315 KCNA1: (KCNA1) VOLTAGE-GATED Q09470 NM OOO217 POTASSIUM CHANNEL PROTEINKV1.1 (HUKI) (HBK1). KCNA3: (KCNA3 OR HGK5) VOLTAGE P22001 NM OO2232 GATED POTASSIUM CHANNEL PROTEIN KV1.3 (HPCN3) (HGK5) (HUKIII) (HLK3) (MK3) (RCK3) (KV3). KCNA4: (KCNA4) VOLTAGE-GATED P224.59 NM O02233 POTASSIUM CHANNEL PROTEINKV1.4 (HK1) (HPCN2) (HBK4) (HUKII) (RCK4) (RHK1) (RK4). 25.333 KCNA7: (KCNA7) POTASSIUMVOLTAGE NM O31886 GATED CHANNEL, SHAKER-RELATED SUBFAMILY, MEMBER 7) (KCNC7). KCNB1: (KCNB1) VOLTAGE-GATED Q14721 Q14193 NM OO4975 POTASSIUM CHANNEL PROTEINKV2.1 (DHK1) H-DRK1 K(+) CHANNEL (DJ791K14.1) (POTASSIUM VOLTAGE GATEDCHANNEL, SHAB-RELATED SUBFAMILY, MEMBER 1) (SHAB). 25339 KCNB2: (KCNB2) VOLTAGE-GATED NM 004770 POTASSIUM CHANNEL PROTEINKV2.2, SHAB-RELATED SUBFAMILY, MEMBER 2 (CDRK). KCNC1: (KCNC1) VOLTAGE-GATED P485.47 NM OO4976 POTASSIUM CHANNEL PROTEINKV3.1 (KV4) (NGK2). 25351 KCND1: (KCND1) SHAL-TYPE POTASSIUM NM OO4979 CHANNEL (VOLTAGE-GATED POTASSIUM CHANNEL KV4.1) (MSHAL). 25354 KCND2: (KCND2 OR KIAA1044) VOLTAGE NM 012281 GATED POTASSIUM CHANNELKV4.2 (SHAL1) (RK5) POTASSIUM CHANNEL PROTEINRKS.

KCNH2: (KCNH2 OR HERG OR HERG1 OR NM OOO238 ERG OR ERG1) POTASSIUMVOLTAGE NM 172056 GATED CHANNEL SUBFAMILYH MEMBER NM 172057 2 (ETHER-A-GO-GO RELATED GENE POTASSIUM CHANNEL 1) (H-ERG) (ERG1) (ETHER-A-GO-GO RELATED PROTEIN 1) (EAG RELATED PROTEIN 1) (EAG HOMOLOG) (MERG) (MERG1) (R-E KCNJ1: (KCNJ1 ORROMK1) ATP NM OOO220 SENSITIVE INWARD RECTIFIER NM 153764 POTASSIUM CHANNEL 1 (POTASSIUM NM 153765 HANNEL, INWARDLY RECTIFYING, NM 153766 UBFAMILY J, MEMBER 1) (ATP NM 153767 EGULATED POTASSIUM CHANNEL ROM ) (KIR1.1) ROM-K POTASSIUM CHANNEL ROTEIN ISOFORM ROMK2 (KAB-1). KCNJ10: (KCNJ10) ATP-SENSITIVE NM 002241 NWARD RECTIFIERPOTASSIUM CHANNEL 10 (POTASSIUM CHANNEL, NWARDLY RECTIFYING, SUBFAMILY J, MEMBER 10) (INWARD RECTIFIERK+ CHANNEL KIR1.2) (ATP-DEPENDENT NWARDLY RECTIFYING POTASSIUM CHANNEL KIR4.1). 25372 KCNJ15: (KCNJ15 OR KCNJ14) ATP Q96L28 Q99712 NM OO2243 SENSITIVE INWARD RECTIFIER Q99446 O00564 NM 170736 POTASSIUM CHANNEL 15 (POTASSIUM NM 170737 CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 15) (INWARD RECTIFIER K+ CHANNEL KIR4.2) (KIR1.3). 25.375 KCNJ16: (KCNJ16) INWARD RECTIFIER NM 018658 POTASSIUM CHANNEL 16 (POTASSIUM NM 170741 US 2008/O 159999 A1 Jul. 3, 2008 61

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 CHANNEL, INWARDLY RECTIFYING, NM 170742 SUBFAMILY J, MEMBER 16) (INWARD RECTIFIER K+ CHANNEL KIR5.1) (BIR9). 25378 KCNJ2: (KCNJ2 OR HIRK1) INWARD P632S2P48049 NM OOO891 RECTIFIERPOTASSIUM CHANNEL 2 O15110 (POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER2) (INWARD RECTIFIERK+ CHANNEL KIR2.1) (CARDIAC INWARD RECTIFIER POTASSIUM CHANNEL) (IRK1) (RBL-IRK1). KCNJ8: (KCNJ8) ATP-SENSITIVE INWARD Q15842 OOO657 NM 004982 RECTIFIERPOTASSIUM CHANNEL 8 (POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 8) (INWARDLY RECTIFIER K+ CHANNEL KIR6.1) (UKATP-1). 25387 KCNJN1-KCNJ12: (KCNJN1) INWARD NM 021012 RECTIFYING. K. CHANNEL NEGATIVE REGULATOR KIR2.2V. (KCNJ12 OR IRK2) ATP-SENSITIVE INWARD RECTIFIER POTASSIUM CHANNEL 12 (POTASSIUM CHANNEL, INWARDLY RECTIFYING, BFAMILY J, MEMBER 12) INWARDRECTIFIER K+ CHANNEL KIR2.2). 25390 NK1: (KCNK1 OR TWIK1 OR HOHO1 OR O00180 Q13307 NM 002.245 0.65 % NO1) POTASSIUM CHANNEL BFAMILY K MEMBER 1 (INWARD ECTIFYING POTASSIUM CHANNEL ROTEIN TWIK-1) (POTASSIUM CHANNEL KCNO1) PUTATIVE POTASSIUM CHANNEL TWIK. 25411 KCNK2: (KCNK2 OR TREK1 OR TREK) NM O14217 POTASSIUM CHANNEL SUBFAMILYK MEMBER2 (OUTWARD RECTIFYING POTASSIUM CHANNEL PROTEIN TREK-1) (TREK-1 K+ CHANNEL SUBUNIT) (TWO PORE POTASSIUM CHANNELTPKC1)2P DOMAIN POTASSIUM CHANNEL KCNK2. 25414 KCNK3: (KCNK3 ORTASK) POTASSIUM O14649 NM OO2246 CHANNEL SUBFAMILYK MEMBER3 (ACID-SENSITIVE POTASSIUM CHANNEL PROTEIN TASK) (TWIK-RELATED ACID SENSITIVE K+ CHANNEL). 25417 KCNK4: (KCNK4 ORTRAAK) POTASSIUM NM 016611 1.26 % CHANNEL SUBFAMILYK MEMBER 4 NM 033310 (TWIK-RELATED ARACHIDONIC ACID NM 033311 STIMULATED POTASSIUM CHANNEL PROTEIN) (TRAAK) MECHANOSENSITIVE TANDEMPORE POTASSIUM CHANNEL. 2S420 KCNK5: (KCNK5 OR TASK2) POTASSIUM O95279 NM 003740 CHANNEL SUBFAMILYK MEMBERS (ACID-SENSITIVE POTASSIUM CHANNEL PROTEIN TASK-2) (TWIK-RELATED ACID SENSITIVE K+ CHANNEL 2). KCNK7: (KCNK7) POTASSIUM CHANNEL NM O05714 SUBFAMILY K MEMBER7 (KCNK8 OR NM 033347 KCNK6 ORDPKCH3 OR KNOT1) NM 033348 POTASSIUM CHANNEL SUBFAMILYK NM 033455 MEMBER 8 (PUTATIVE POTASSIUM NM 033456 CHANNEL DP3) (DOUBLE-PORE K+ CHANNEL3) (NEUROMUSCULAR TWO DOMAIN POTASSIUM CHANNEL). 25441 KCNQ4: (KCNQ4) POTASSIUMVOLTAGE NM 004700 GATED CHANNEL SUBFAMILY KQT NM 1721.63 MEMBER4 (VOLTAGE-GATED POTASSIUM CHANNEL SUBUNIT KV7.4) (POTASSIUM CHANNEL ALPHASUBUNIT KVLQT4) (KQT-LIKE 4). 25444 KCNQ5: (KCNQ5) POTASSIUMVOLTAGE NM O19842 GATED CHANNEL SUBFAMILY KQT MEMBER5 (VOLTAGE-GATED POTASSIUM US 2008/O 159999 A1 Jul. 3, 2008 62

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 CHANNEL SUBUNIT KV7.5) (POTASSIUM CHANNEL ALPHASUBUNIT KVLQT5) (KQT-LIKE 5). KCNS1: (KCNS1 OR KV9.1) DJ211D12.1 NM OO2251 (POTASSIUM VOLTAGE-GATED CHANNEL, DELAYED-RECTIFIER, SUBFAMILYS, MEMBER 1) (DELAYED-RECTIFIER K+ CHANNEL ALPHASUBUNIT) (POTASSIUM CHANNEL ALPHASUBUNIT). KCNS2: (KCNS2 OR KV9.2) POTASSIUM NM 020697 CHANNEL ALPHA SUBUNIT (KIAA1144). KCNH3: (KCNH3 OR KIAA1282) NM 012284 POTASSIUMVOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER3. (ETHER-A-GO GO-LIKE POTASSIUM CHANNEL 2) (ELK CHANNEL 2) (ELK2) (BRAIN-SPECIFIC EAG-LIKE CHANNEL 1) (BEC1). KIAA1535: (KIAA1535) (HCN3 OR HAC3) NM 020897 HYPERPOLARIZATION-ACTIVATED CATION CHANNEL, HAC3. KIR2.4: (KIR2.4 OR KCNJ14) INWARD NM 013348 RECTIFIERPOTASSIUM CHANNEL NM 170720 (INWARDLY RECTIFYING POTASSIUM CHANNEL KIR2.4). 255.25 SCN5A: (SCNSA) SODIUM CHANNEL Q14524 NM 000335 PROTEIN, CARDIAC MUSCLE ALPHA NM 198056 SUBUNIT (HH1). 2558O CLCN2: (CLCN2) CHLORIDE CHANNEL NM 004366 PROTEIN 2 (CLC-2). 25583 CLCN4: (CLCN4) CHLORIDE CHANNEL NM OO1830 PROTEIN 4 (CLC-4) (CLCN4-2) PUTATIVE CHLORIDE CHANNEL (SIMILAR TOMM C LCN4-2). 25586 C LCN5: (CLCN5 OR CLCK2) CHLORIDE NM 000084 C HANNEL PROTEIN 5 (CLC-5). 25793 MYOCD: (MYOCD OR MYCD OR SRFCP OR NM 153604 BSAC2) MYOCARDIN (SRJF CO-FACTOR PROTEIN) (BASICSAP COILED-COIL TRANSCRIPTION ACTIVATOR2). 25908 CTNND2: (CTNND2 OR NPRAP) CATENIN NM OO1332 DELTA-2 (DELTA-CATENIN) (NEURAL PLAKOPHILIN-RELATED ARM-REPEAT PROTEIN) (NPRAP) (NEUROJUNGIN) (GT24). 25932 HIST1H2AC: (HIST1H2AC OR H2AFL) NM 003512 HISTONE H2A.L. (H2A/L). 25938 HMGIC: (HMGA2 OR HMGIC) HIGH NM OO3483 1.38.22% MOBILITY GROUP PROTEIN HMGI-C (HIGH MOBILITY GROUP AT-HOOK 2). PBXIP1: (PBXIP1 OR 4732463H2ORIK) PRE NM 020524 B-CELL LEUKEMIA TRANSCRIPTION FACTORINTERACTING PROTEIN 1 (HEMATOPOIETIC PBX-INTERACTING PROTEIN) (FLJ12435) (FLJ13157) (HPIP) (HPBXIP). 261.75 GPC4: (GPC4) GLYPICAN-4 PRECURSOR (K- NM OO1448 GLYPICAN).

26.188 KCNQ2: (KCNQ2) VOLTAGE-GATED NM OO4518 POTASSIUM CHANNEL PROTEIN KQT NM 172106 LIKE 2 (NEUROBLASTOMA-SPECIFIC NM 172107 POTASSIUM CHANNEL PROTEIN). NM 172108 NM 172109 26268 VAPA: (VAPA ORVAP33) VESICLE NM 003574 ASSOCIATED MEMBRANE PROTEIN NM 194434 ASSOCIATED PROTEIN A (VAMP ASSOCIATED PROTEINA) (VAMP-A) (VAP US 2008/O 159999 A1 Jul. 3, 2008 63

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 A) (33 KDA VAMP-ASSOCIATED PROTEIN) (VAP-33). 26313 CACNB2: (CACNB2 OR CACNLB2 OR NM 000724 MYSB) DIHYDROPYRIDINE-SENSITIVE L NM 201570 TYPE, CALCIUM CHANNEL BETA-2 NM 201571 SUBUNIT (CAB2) (VOLTAGE-DEPENDENT NM 201572 CALCIUM CHANNEL BETA-2 SUBUNIT) NM 201590 (LAMBERT-EATON MYASTHENIC NM 201593 SYNDROME ANTIGENB) (MYSB). NM 2 26316 CACNB4: (CACNB4 OR CACNLB4) NM 000726 DIHYDROPYRIDINE-SENSITIVE L-TYPE, CALCIUM CHANNEL BETA-4 SUBUNIT (CAB4) (VOLTAGE-DEPENDENT CALCIUM CHANNEL BETA-4 SUBUNIT). 26388 FGF23: (FGF23 OR HYPF) FIBROBLAST NM 020638 1.30 % GROWTH FACTOR-23 PRECURSOR(FGF 23) (TUMOR-DERIVED HYPOPHOPHATEMIA INDUCING FACTOR). 26497 KCNE 1: (KCNE1) ISK SLOW VOLTAGE NM OOO219 GATED POTASSIUM CHANNEL PROTEIN (MINIMAL POTASSIUM CHANNEL) (MINK). 26SOO KCNE2: (KCNE2) MINIMUM POTASSIUM NM 1722O1 ON CHANNEL-RELATED PEPTIDE 1 (MIRP1) (MINK-RELATED PEPTIDE 1). KCNE3: (KCNE3) MINIMUM POTASSIUM NM 005472 ON CHANNEL-RELATED PEPTIDE 2 (MIRP2) (MINK-RELATED PEPTIDE 2). 26623 SCN1B: (SCN1B) SODIUM CHANNEL BETA Q07699 NM OO1037 SUBUNIT PRECURSOR. NM 199037 26660 TGFBR3: (TGFBR3) TGF-BETA RECEPTOR NM OO3243 TYPE III PRECURSOR (TGFR-3) (BETAGLYCAN). 26941 MYH6: (MYH6 OR MYHCA) MYOSIN NM OO2471 HEAVY CHAIN, CARDIAC MUSCLE ALPHA SOFORM (MYHC-ALPHA). 26.951 NME2: (NME2 OR NM23B) NUCLEOSIDE P22392 NM 001018136 1.48.13% DIPHOSPHATE KINASEB (EC 2.74.6) (NDK NM 001018137 B) (NDP KINASEB) (P18). NM 001018138 NM 001018139 NM OO2512 26966 PRPH: (PRPH) PERIPHERIN (PRPH1). NM OO6262 DERMO1: (TWIST2 ORDERMO1) TWIST NM 057179 RELATED PROTEIN 2 (DERMIS EXPRESSED PROTEIN 1) (DERMO-1). 27246 PTN: (PTN OR NEGF1 OR HBNF1) P21246 NM 002825 1.60, -96 PLEIOTROPHIN PRECURSOR (PTN) (HEPARIN-BINDING GROWTH ASSOCIATED MOLECULE) (HB-GAM) (HEPARIN-BINDING GROWTH FACTOR8) (HBGF-8) (OSTEOBLAST SPECIFIC FACTOR ) (OSF-1) (HEPARIN-BINDING NEURITE OUTGROWTH PROMOTING FACTOR1) (HBNF 27251 PTTG HUMAN: (PTTG1 OR EAP1 ORPTTG NM 004219 1.60.6% ORTUTR1) AND (PTTG2) AND (PTTG3)) NM OO6607 SECURIN (PITUITARY TUMOR NR OO2734 TRANSFORMING PROTEIN 1) (TUMOR TRANSFORMING PROTEIN 1) (ESP1 ASSOCIATED PROTEIN) (HPTTG) (PITUITARY TUMORTRANSFORMING GENE PROTEIN 2) (PITUITARY TUMOR TRANSFO 27255 RPS24: (RPS24 OR RPS19) 40S RIBOSOMAL P62847 P16632 NM 001026 1.06.8% PROTEINS24 (S19). NM 033022 ALPL: (ALPL) ALKALINE PHOSPHATASE, NM 000478 TISSUE-NONSPECIFIC ISOZYME PRECURSOR (EC 3.1.3.1) (AP-TNAP) (LIVER/BONE/KIDNEY ISOZYME) (TNSALP) (AKP2 ORAKP-2). 27579 PTHLH: (PTHLH ORPTHRP) Q15251 P12272 NM 002820 O.31.0% PARATHYROID HORMONE-RELATED NM 198964 US 2008/O 159999 A1 Jul. 3, 2008 64

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 PROTEIN PRECURSOR (PTH-RP) (PTHRP) NM 198965 CONTAINS: OSTEOSTATIN (PTHRP107-139) NM 198966 PARATHYROID HORMONE-LIKE HORMONE. 27728 JADE1 1: (PHF17 ORJADE1) NM 19932O HYPOTHETICAL PROTEIN KIAA1807 (PHD ZINC FINGER PROTEIN JADE-1) (FLJ14714) (FLJ22479) (FLJ45397) (JADE1L) (FLT90505).

27741 MAD2L1: (MAD2L1 OR MAD2 OR MAD2A) NM 002358 MITOTICSPINDLEASSEMBLY CHECKPOINT PROTEIN MAD2A (MAD2 LIKE 1). 27762 SOX11: (SOX11 OR SOX-11) P35716 NM OO3108 TRANSCRIPTION FACTORSOX-11. 27831 CITED2: (CITED2 OR MRG1) CBP/P300 Q99967 O95426 NM OO6079 INTERACTING TRANSACTIVATOR2 (MSG RELATED PROTEIN 1) (MRG1 PROTEIN) (P35SRJ). 27864 TNNT1: (TNNT1 ORTNT) TROPONINT, O95472 Q16061 NM OO3283 SLOWSKELETAL MUSCLE ISOFORMS P13805 (SLOWSKELETAL MUSCLE TROPONINT). 27870 ANGPT1: (ANGPT1 OR KIAA0003) Q15389 NM 001146 ANGIOPOIETIN-1 PRECURSOR (ANG-1). NM 139290 27873 ANGPT2: (ANGPT2) ANGIOPOIETIN-2 NM 001147 PRECURSOR (ANG-2). 27964 ALPPL2 HUMAN: (ALPPL2 OR ALPPL) NM 031313 ALKALINE PHOSPHATASE, PLACENTAL LIKE PRECURSOR (EC 3.1.3.1) (NAGAO ISOZYME) (GERM-CELLALKALINE PHOSPHATASE) (PLAP-LIKE) (ALP-1). 27965 ALPP HUMAN: (ALPP OR PLAP) ALKALINE P05187 PO5188 NM OO1632 1.SS.41% PHOSPHATASE, PLACENTALTYPE 1 PO6861 PRECURSOR (EC 3.1.3.1) (PLAP-1) (REGAN Q96DB7 ISOZYME) (ALKALINE PHOSPHATASE, PLACENTALTYPE 3 PRECURSOR). 281 60 SOX5: (SOX5 OR SOX-5) TRANSCRIPTION NM OO6940 FACTORSOX-5. NM 152989 NM 178010

28292 CHI3L2 HUMAN: (CHI3L2) CHITINASE3 NM 001025197 LIKE PROTEIN 2 PRECURSOR (YKL-39) NM 001025 199 (CHONDROCYTE PROTEIN39). NM 004.000 2832O KPNA2: (KPNA2 OR RCH1 OR SRP1) NM 002266 IMPORTINALPHA-2 SUBUNIT (KARYOPHERIN ALPHA-2 SUBUNIT) (SRP1 ALPHA) (RAG COHORT PROTEIN 1). 28475 LAPTM4B: (LAPTM4B ORLAPTM4BETAOR NM O18407 1.12.19% DKFZP586E1124) LYSOSOMAL ASSOCIATED TRANSMEMBRANE PROTEIN 4 BETA (NT2RM1000066) (LC27) (INTEGRAL MEMBRANE TRANSPORTER) (HYPOTHETICAL PROTEIN PSEC0001). NPPA: (NPPA OR PND) ATRIAL PO1160 Q13766 NM OO6172 NATRIURETIC FACTOR PRECURSOR (ANF) (ATRIAL NATRIURETIC PEPTIDE) (ANP) (PREPRONATRIODILATIN). 28658 RPL24: (RPL24) 60S RIBOSOMAL PROTEIN NM OOO986 1.32.13% L24 (L30). 28891 DAB1: (DAB1) DISABLED HOMOLOG 1. NM 021080 2891S OLIG1: (OLIG1) OLIGODENDROCYTE NM 138983 TRANSCRIPTION FACTOR 1 (OLIGO1) (OLIGODENDROCYTE-SPECIFIC BHLH TRANSCRIPTION FACTOR 1). US 2008/O 159999 A1 Jul. 3, 2008 65

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 28921 RELN: (RELNORRL) REELIN PRECURSOR NM O05045 (EC 3.4.21- ) (REELER PROTEIN). NM 173054

28924 ROBO1: (ROBO1 ORDUTT1) DUTT1 NM OO2941 PROTEIN. NM 133631 28937 TUBB3 HUMAN: (TUBB3 ORTUBB4) NM OO6086 1.46.9% TUBULIN BETA-3 CHAIN (TUBULIN BETA II) (TUBULIN BETA-4). 291.97 LEFTY2 HUMAN: (LEFTY2 OREBAF OR NM OO3240 107.7% TGFB4 OR LEFTA OR LEFTYA) TLEFT RIGHT DETERMINATION FACTOR 2 PRECURSOR (PROTEIN LEFTY-2) (LEFT RIGHT DETERMINATION FACTORA) (PROTEIN LEFTY-A) (TRANSFORMING GROWTH FACTOR BETA-4) (TGF-BETA-4) (ENDOMETRIAL BLEEDING-ASSOCIAT 29198 LEFTY1 HUMAN: (LEFTY1 OR LEFTB OR O75610 NM 020997 LEFTYB). LEFT-RIGHT DETERMINATION FACTOR 1 PRECURSOR (PROTEIN LEFTY ) (LEFT-RIGHT DETERMINATION FACTOR B) (PROTEIN LEFTY-B). 29221 NCAM2: (NCAM2 OR NCAM21) NEURAL O15394 NM OO4540 1.20.15% CELL ADHESIONMOLECULE 2 PRECURSOR (N-CAM 2). 29310 SNAI2: (SNAI2 OR SLUG OR SLUGH)ZINC O43623 NM OO3068 1.07.24% FINGER PROTEIN SLUG (NEURAL CREST TRANSCRIPTION FACTORSLUG) (SNAIL HOMOLOG 2). 29322 SST: (SSTORSMST) SOMATOSTATIN P61278. PO1166 NM 001048 PRECURSOR CONTAINS: ANTRIN; SOMATOSTATIN-28; SOMATOSTATIN-14). 29328 TH: (THORTYH) TYROSINE 3 P07101 Q15585 NM OOO360 MONOOXYGENASE (EC 1.14.16.2) Q15588 Q15589 NM 199292 (TYROSINE 3-HYDROXYLASE) (TH). NM 199293 29367 NEUROG2: (NEUROG2 OR NGN2ORATH4 NM 024019 1.11–% ORATOH4 ORATH4A) NEUROGENIN 2 (ATONAL PROTEIN HOMOLOG 4) (HELIX LOOP-HELIX PROTEIN MATH-4A) (MATH4A). 29371 DLX1: (DLX1) HOMEOBOX PROTEINDLX NM 178120 2.94.75 CEBPA 3: (CEBPA) CCAAT/ENHANCER NM 004364 BINDING PROTEIN ALPHA (C/EBPALPHA). 299.09 GHA1-IGHA2 M HUMAN: (IGHA1) IG 184707 ALPHA-1 CHAIN C REGION (IGHA2) (IG ALPHA-2 CHAIN C REGION). PROM1: (PROM1 OR PROML1 OR PROMOR O43490 NM OO6017 CD133 ORAC133) PROMININ 1 PRECURSOR (PROMININ-LIKE PROTEIN 1) (ANTIGEN AC133) (CD133 ANTIGEN). L30: (L30) 60S RIBOSOMAL PROTEIN L30 NM 016304 SOLOG (MY024 PROTEIN) (RPL24) (CHROMOSOME 15 OPEN READING FRAME 5).

SNRPF: (SNRPF OR PBSCF) SMALL NM 003095 NUCLEARRIBONUCLEOPROTEINF (SNRNP-F) (SM PROTEINF) (SM-F) (SMF). 30327 ACTC: (ACTC ORACTC1) ACTIN, ALPHA NM OO51.59 CARDIAC. CFC 1: (CFC1) CRYPTIC PROTEIN NM 032545 PRECURSOR CHF 1: (CHF1 OR HRT2 OR HEY2 OR HESR2) NM 012259 BASICHELIX-LOOP-HELIX FACTOR1 (BASIC-HELIX-LOOP-HELIX PROTEIN) (HES-RELATED REPRESSOR PROTEIN 1 HERP1) (HAIRY AND ENHANCER OF SPLIT RELATED2) (CARDIOVASCULAR BASIC HELIX-LOOP-HELIXFACTOR1, CHF1). US 2008/O 159999 A1 Jul. 3, 2008 66

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 MMRN: (MMRN ORECM) ENDOTHELIAL NM OO7351 CELL MULTIMERIN PRECURSOR. PODXL: (PODXL OR PCLP1 ORPCLP) OOOS92 NM OO5397 PODOCALYXIN-LIKE PROTEIN 1 PRECURSOR 30353 ROBO4: (ROBO4 OR 1200012D01 RIK) NM O19055 MAGIC ROUNDABOUT (FLJ14946) (FLTO0236) (FLJ20798) (FLJ21542).

30355 TEAD1: (TEAD1 ORTEF1 ORTEF-1 OR NM 021961 TCF13) TRANSCRIPTIONAL ENHANCER FACTOR TEF-1 (TEA DOMAIN FAMILY MEMBER 1) (TEAD-1) (PROTEIN GT-IIC) (TRANSCRIPTION FACTOR 3) (NTEF-1). TNNT2: (TNNT2) TROPONIN T, CARDIAC NM OOO364 MUSCLE ISOFORMS (TNTC). ZFPM2: (ZFPM2 OR FOG2 ORFOG-2) FOG2 NM 012082 TRANSCRIPTION FACTOR (FRIEND OF GATA2) (B330005D23RIK).

ITGAX: (ITGAXORCD11C) NTEGRIN NM OOO887 ALPHA-X PRECURSOR (LEUKOCYTE ADHESION GLYCOPROTEIN P150,95 ALPHACHAIN) (LEUKOCYTE ADHESION RECEPTORP150,95) (CD11C) (LEUM5). TGFB1: (TGFB1 ORTGFB) TRANSFORMING NM OOO660 O.71.17% GROWTH FACTOR BETA 1 PRECURSOR

30442 P106OO NM OO3239 O.94.23% TRANSFORMING GROWTH FACTOR BETA 3 PRECURSOR (TGF-BETA3). PF4-PF4V1 HUMAN: (SCYB4 ORPF4) PO2776 P1072O NM 002619 PLATELET FACTOR4 PRECURSOR (PF-4) NM OO2620 (ONCOSTATINA) (IROPLACT) (PF4V1 OR SCYB4V1) (PLATELET FACTOR4 VARIANT PRECURSOR) (PF4VAR1) (PF4ALT) 3.0523 CLF-1: (CLF-1) CYTOKINE-L KEFACTOR-1 NM 004750 PRECURSOR (SIMILAR TO CYTOKINE RECEPTOR-LIKE FACTOR1) (ZCYTOR5) (CLASS I CYTOKINE RECEPTOR) (CRLF1 ORCRLM3) (CYTOKINE RECEPTOR LIKE MOLECULE3 PRECURSOR). FGF20: (FGF20) FIBROBLAST GROWTH NM 019851 FACTOR-20 (FGF-20). 30615 SDF2: (SDF2) STROMAL CELL-DERIVED NM OO6923 O.89.8% FACTOR2 PRECURSOR (SDF-2). 30624 BMP11: (GDF11 OR BMP11) NM OO5811 1.20.32% GROWTHADIFFERENTIATION FACTOR 11 PRECURSOR (BONE MORPH OGENETIC PROTEIN 11). 30632 FGF17: (FGF17) FIBROBLAST GROWTH NM OO3867 FACTOR-17 PRECURSOR (FGF-17). 3063S FGF18: (FGF18) FIBROBLAST GROWTH O76093 NM O03862 FACTOR-18 PRECURSOR (FGF-18). NM 03.3649 30637 RHST OR HSTF1 ORKS3) NM OO2007 FIBROBLAST GROWTH FACTOR-4 PRECURSOR (FGF-4) (HEPARIN SECRETORYT RANSFORMING PROTEIN) (HST-1) (HST) ( TRANSFORMING PROTEIN KS3) (HBGF-4). 306.71 RARA1: (RARAORNR1B1) RETINOIC ACID P10276 P78456 NM 000964 RECEPTORAL PHA (RAR-ALPHA). Q13440 Q13441 NM 001024.809 Q96S41 NM OO1033603 Q9NQSO 30683 FN1 REPEAT TO6: (FN1 ORFN) PO2751 O95609 NM 002026 O.S8.2% FIBRONECTIN PRECURSOR (FN) (COLD O95610 Q14312 NM 212474 NSOLUBLE G LOBULIN) (CIG). Q14325 Q14326 NM 212475 US 2008/O 159999 A1 Jul. 3, 2008 67

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 NM 212476 NM 212478 NM 212482 30686 FN1 REPEATA: (FN1 ORFN) NM 002026 0.24.2% FIBRONECTIN PRECURSOR (FN) (COLD NM 212474 (NSOLUBLE GLOBULIN) (CIG). NM 212475 NM 212476 NM 212478 NM 212482 30689 FN1 REPEAT-B: (FN1 ORFN) NM 002026 O.19.8% FIBRONECTIN PRECURSOR (FN) (COLD NM 212474 (NSOLUBLE GLOBULIN) (CIG). NM 212475 NM 212476 NM 212478 NM 212482 30808 CNTFR: (CNTFR) CILIARY NEUROTROPHIC P26992 NM OO1842 FACTOR RECEPTOR ALPHAPRECURSOR NM 147164 (CNTFRALPHA). 30815 GATA5: (GATA5) TRANSCRIPTION NM 080473 FACTOR GATA-5 (GATA BINDING FACTOR-5). 30954 ACRP: (ACRP ORCTNNAL1) ALPHA NM 003798 1.441.1% CATENIN-LIKE PROTEIN.

30957 ADH4: (ADH4) ALCOHOL NM OOO670 DEHYDROGENASE CLASS II PICHAIN PRECURSOR (EC 1.1.1.1). 30963 ARHGAP9: (ARHGAP9). RHO-GTPASE NM 032496 ACTIVATING PROTEIN (FLJ35444) (RGL1) (DKFZP667F149) (AUO43488).

3.0969 BUB1B: (BUB1B OR MAD3L OR BUBR1) NM 001211 MITOTIC CHECKPOINT SERINETHREONINE-PROTEINKINASE BUB1 BETA (EC 2.7.1. ) (HBUBR1) (MAD3/BUB1-RELATED PROTEIN KINASE) (MITOTIC CHECKPOINT KINASE MAD3L). 30972 UB3: (BUB3) MITOTIC CHECKPOINT O43684 O43685 NM OO4725 ROTEINBUB3. 30975 A14: (CA14) CARBONIC ANHYDRASE XIV NM 012113 RECURSOR (EC 4.2.1.1) (CARBONATE E. EHYDRATASE XIV) (CA-XIV). 30978 CCAP: (SDCCAG8 ORCCCAP) NM OO6642 ENTROSOMAL COLON CANCER UTOANTIGEN PROTEIN (HSPCO85) (NY -8) (2700048G21RIK) (5730470G24RIK) LINKY). 30981 DO1: (CDO1) CYSTEINE DIOXYGENASE NM OO1801 TYPEI (EC 1.13.11.20) (CDO) (CDO-I). 30984 CHI3L1: (CHI3L1) CHITINASE-3 LIKE NM OO1276 ROTEIN 1 PRECURSOR(CARTILAGE LYCOPROTEIN-39) (GP-39) (39 KDA YNOVIAL PROTEIN) (YKL-40). 30987 PN2: (CPN2). CARBOXYPEPTIDASEN 83 NM OO1309 1.40.25% DA CHAIN (CARBOXYPEPTIDASEN EGULATORY SUBUNIT) ARBOXYPEPTIDASEN POLYPEPTIDE 2). 3.0990 CRM1: (CRM1) CRM1 PROTEIN (XPO1) NM OO3400 1.04.14% (EXPORTIN 1) (EXPRESSED SEQUENCE AA420417) (NUCLEAR EXPORT FACTOR RM1). 30993 RYL1: (CRYL1) LAMBDA-CRYSTALLIN NM O15974 1.39.29% OMOLOG. 30996 RYZ: (CRYZ) QUINONE NM OO1889 O.88.26% XIDOREDUCTASE (EC 1.6.5.5) (NADPH: QUINONE REDUCTASE) (ZETA RYSTALLIN).

US 2008/O 159999 A1 Jul. 3, 2008 69

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 31090 KIAA1698: (KIAA1698) HYPOTHETICAL NM 030628 PROTEIN KIAA1698 (1110055N21RIK). 31093 KS: (KS) KIDNEY-SPECIFIC PROTEIN NM 182617 (XENOBIOTIC/MEDIUM-CHAIN FATTY ACID: COALIGASE) (FLJ26434) (FLJ38720). 31096 MAD1: (MAD1L1 OR MAD1) MITOTIC NM 03550 1.43.68% CHECKPOINT PROTEIN (MAD1 (MITOTIC ARREST DEFICIENT, YEAST, HOMOLOG)- LIKE 1) (TXBP181) (MAD1A) (MAD1B). 31099 MAD2L2: (MAD2L2 OR MAD2B OR REV7) NM OO6341 MITOTICSPINDLEASSEMBLY CHECKPOINT PROTEIN MAD2B (MAD2 LIKE2) (HREV7) (2310033C13RIK). 31.102 MAT1A: (MAT1A ORMATA1 OR AMS1) S NM 000429 ADENOSYLMETHIONINE SYNTHETASE ALPHA AND BETA FORMS (EC 2.5.1.6) (METHIONINE ADENOSYLTRANSFERASE) (ADOMETSYNTHETASE) (MAT-I/III). 311 OS MAWBP: (MAWBP) MAWD BINDING NM 022129 PROTEIN (UNKNOWN PROTEIN 32 FROM 2D-PAGE OF LIVERTISSUE) (PROBABLE OXIDOREDUCTASE 0610038KO3RIK) (PROBABLE OXIDOREDUCTASE 3110049J23RIK). 31.108 MGC16491; (4732473B16RIKORAUO45678) NM 052943 HYPOTHETICAL PROTEIN (MGC16491). 31112 NANOG: (NANOG) HOMEOBOX NM O24865 TRANSCRIPTION FACTOR NANOG (FLJ12581) (FLJ40451) (EMBRYONIC STEM CELL SPECIFIC HOMEOBOX PROTEIN). 31114 NOP5: (NOP5) NUCLEOLAR PROTEIN NOP5 NM O15934 (NUCLEOLAR PROTEIN 5) (NOP58) (HSPC12O) (NOLS) (SIKSIMILAR PROTEIN). 31117 NUMB: (NUMB) NUMB PROTEIN NM 003744 HOMOLOG (H-NUMB) (PROTEIN S171).

31120 PCPB: (PCPB OR CPB2 OR TAFI) PCPB NM OO1872 PROTEIN (CARBOXYPEPTIDASE B2 NM 016413 (PLASMA)) (CARBOXYPEPTIDASE B-LIKE PROTEIN) (CPB2) (BA139H14.2) (CARBOXYPEPTIDASER) (THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR) (1110032P04RIK PROTEIN) (CARBOXYPEPTIDASEU). 31.123 PON1: (PON1 OR PON) SERUM P27169 Q16052 NM 0004.46 O.73, 90 PARAOXONASE/ARYLESTERASE 1 (EC 3.1.1.2) (EC 3.1.8.1) (PON 1) (SERUM ARYLDIALKYLPHOSPHATASE 1) (A- ESTERASE 1) (AROMATIC ESTERASE 1) (K- 45). 31126 PON3: (PON3) SERUM NM OOO940 PARAOXONASE/ARYLESTERASE 3 (EC 3.1.1.2) (EC 3.1.8.1) (PON3) (SERUM ARYLDIALKYLPHOSPHATASE 3) (A- ESTERASE 3) (AROMATIC ESTERASE 3). 31129 PPP2R1B 1: (PPP2R1B) NM 002716 SERINETHREONINE PROTEIN PHOSPHATASE 2A, 65 KDA REGULATORY SUBUNITA, BETA ISOFORM (PP2A, SUBUNITA, PR65-BETA ISOFORM) (PP2A, SUBUNITA, R1-BETA ISOFORM) (TRANSCRIPTVARIANT 1). 31,132 PPP2R1B 2: (PPP2R1B) NM 181699 SERINETHREONINE PROTEIN US 2008/O 159999 A1 Jul. 3, 2008 70

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 PHOSPHATASE 2A, 65 KDA REGULATORY SUBUNITA, BETA ISOFORM (PP2A, SUBUNITA, PR65-BETA ISOFORM) (PP2A, SUBUNITA, R1-BETA ISOFORM) (TRANSCRIPTVARIANT 2). PROX1: (PROX1) HOMEOBOX PROSPERO NM OO2763 LIKE PROTEIN PROX1 (PROX 1). REC1: (REC1 OR RAD1A OR HRAD1) CELL NM 002853 CYCLE CHECKPOINT PROTEIN HRAD1 NM 133282 (DNA REPAIR EXONUCLEASE) (RAD1 NM 133377 (S. POMBE) HOMOLOG) (RAD1 HOMOLOG) (S. POMBE). RNASE4: (RNASE4 OR RNS4) NM OO2937 1.06.12% RIBONUCLEASE 4 PRECURSOR (EC 3.1.27- ) (RNASE4). RPL13A: (RPL13A) 60S RIBOSOMAL NM 012423 1.19.14% PROTEIN L13A (23 KDA HIGHLY BASIC PROTEIN). SALL2: (SALL2 OR SAL2 OR KIAA0360) NM OO5407 SAL-LIKE PROTEIN 2 (ZINC FINGER PROTEIN SALL2) (HSAL2). SNAI1: (SNAI1 ORSNAH)ZINC FINGER NM OO5985 PROTEINSNAI1 (SNAIL PROTEIN HOMOLOG) (SNAPROTEIN). SOX1: (SOX1). SOX-1 PROTEIN. NM OO5986 SOX10: (SOX10) TRANSCRIPTION FACTOR NM OO6941 SOX-10. SOX13: (SOX13) SOX-13 PROTEIN (TYPE 1 NM 005686 DLABETES AUTOANTIGEN ICA12) (ISLET CELLANTIGEN 12). SOX3: (SOX3) TRANSCRIPTION FACTOR NM OO5634 1.30.31% SOX-3. SOX6: (SOX6) TRANSCRIPTION FACTOR NM 033326 SOX-6.

31,174 SSPN: (SSPN OR KRAG) SARCOSPAN (K- NM 005086 O.87.74% RAS ONCOGENE-ASSOCIATED PROTEIN) (KIRSTEN-RAS-ASSOCIATED PROTEIN). 31.177 TFPI. (TFPIORTFPI1 ORLACI) TISSUE P10646 O9.5103 NM OO6287 1.02 % FACTOR PATHWAY INHIBITOR PRECURSOR (TFPI) (LIPOPROTEIN ASSOCIATED COAGULATION INHIBITOR) (LACI) (EXTRINSIC PATHWAY INHIBITOR) (EPI). TINF2: (TINF2 OR TIN2) TERF1 NM 012461 INTERACTING NUCLEAR FACTOR2 (TRF1 INTERACTING NUCLEAR PROTEIN 2). TM4SF4: (TM4SF4 ORILTMP) NM 004617 TRANSMEMBRANE4SUPERFAMILY, MEMBER4 (INTESTINE AND LIVER TETRASPAN MEMBRANE PROTEIN) (IL TMP). TREM1: (TREM1) TRIGGERING-RECEPTOR NM 018643 1.40.13% TREM1.

FP42: (ZFP42 OR REX1 OR REX-1)ZINC NM 174900 NGER PROTEIN 42 (ZFP-42) (REX-1 ROTEIN) (REDUCED EXPRESSION-1 ROTEIN). FX: (ZFX)ZINC FINGERX NM 003410 1.33.7% HROMOSOMAL PROTEIN. NF206: (ZNF206 ORZSCAN10)ZINC NM 0328.05 1.341.0% ( NGER PROTEIN 206 (ZINC FINGERAND SCAN DOMAIN-CONTAINING PROTEIN 10) (FLJ14549). SOX18: (SOX18) TRANSCRIPTION FACTOR NM 018419 SOX-18. 3.1460 KIAAO152 1: (KIAAO152) HYPOTHETICAL NM 014730 1.39.5% PROTEIN KIAAO152 (2410014AO8RIK). US 2008/O 159999 A1 Jul. 3, 2008 71

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 31466 KIAAO152 3: (KIAAO152) HYPOTHETICAL Q14165 NM 014730 O.98.39% PROTEIN KIAAO152 (2410014AO8RIK). 32O31 TFRC 3PRIME: (TFRC) TRANSFERRIN NM OO3234 O.70.6% RECEPTOR PROTEIN (TFR1) (TR) (TFR) (TRFR) (CD71 ANTIGEN) (T9) (P90).

32O34 TFRC 5PRIME: (TFRC) TRANSFERRIN NM OO3234 1.17.12% RECEPTOR PROTEIN (TFR1) (TR) (TFR) (TRFR) (CD71 ANTIGEN) (T9) (P90).

32488 NPM1: (NPM1 OR NPM) NUCLEOPHOSMIN NM 001004419 (NPM) (NUCLEOLAR PHOSPHOPROTEIN NM OO2520 B23) (NUMATRIN) (NUCLEOLAR PROTEIN NM 013269 NO38). NM 1991.85

32647 TREM2: TRIGGERING RECEPTOR NM 018965 1.26.28% EXPRESSED ON MYELOID CELLS 2. 32676 ARL8: (ARL8) ADP-RIBOSYLATION NM 178815 FACTOR-LIKE PROTEIN 8. 32679 BRIX: (BRIX) RIBOSOME BIOGENESIS NM 018321 1.61.8% PROTEINBRIX.

32682 C20ORF129: (C20ORF129) PROTEIN NM 030919 C2OORF129.

32685 CYP26A1: (CYP26A1 OR CYP26) NM 000783 CYTOCHROME P450 26 (EC 1.14.- : ) (RETINOIC ACID-METABOLIZING CYTOCHROME) (P450RAI) (HP450RAI) (RETINOIC ACID 4-HYDROXYLASE). 32688 EIF4A1: (EIF4A1 OREIF4A OR DDX2A) PO476SP60842 NM 001416 1.2112% EUKARYOTIC INITIATION FACTOR4A-I Q61516 QSU018 (EIF4A-I)(EIF-4A-I). 32691 DH1: (IDH1 OR PICD) ISOCITRATE NM OO5896 O.72.9% DEHYDROGENASE CYTOPLASMIC (EC .1.1.42) (OXALOSUCCINATE DECARBOXYLASE) (IDH) (NADP+- SPECIFICICDH) (IDP). 32694 MPDH2: (IMPDH2OR MPD2) INOSINE-5'- P12268 Q6LEF3 NM 0008.84 1.53.10% MONOPHOSPHATE DE HYDROGENASE 2 (EC 1.1.1.205) (IMP DEH YDROGENASE 2) (IMPDH-II) (IMPD 2). 32700 KIAA1573: (KIAA1573) HYPOTHETICAL NM 020925 PROTEIN KIAA1573 (B430218L07RIK) (DKFZP686L04115) (FL 12509) (FLJ14194). 32703 KIF4A: (KIF4A OR KIF4) CHROMOSOME NM 012310 1.62.26% ASSOCIATED KINESIN (CHROMOKINESIN).

32706 LIN-28: (LIN28 ORLIN 28). HYPOTHETICAL NM O24674 1.19.29% PROTEIN FLJ12457 (RNA-BINDING PROTEIN LIN-28). 32709 LRRN1: (LRRN1 ORNL RR-1) LEUCINE RICH NM 020873 REPEAT PROTEIN 1, NEURONAL (KIAA1497) (NLRR).

32712 MTHFD1: (MTHFD1 ORMTHFD OR MTHFC) NM OO5956 C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC (C1-THFSYNTHASE). US 2008/O 159999 A1 Jul. 3, 2008 72

TABLE 4-continued Array # Geneti Name UniProtitrEMBL RefSeq, 4800038 32715 NBR2 HUMAN: (NBR2) NBR2 PROTEIN O15453 NM OO5821 (NEXT TO BRCA1 GENE 2 PROTEIN). 32716 PPAT: (PPAT OR GPAT) Q06203 NM OO2703 AMIDOPHOSPHORIBOSYLTRANSFERASE PRECURSOR (EC 2.4.2.14) (GLUTAMINE PHOSPHORIBOSYLPYROPHOSPHATE AMIDOTRANSFERASE) (ATASE) (GPAT). 32719 RPL4: (RPL4 ORRPL1) 60S RIBOSOMAL P36578 P39029 NM OOO968 1.37.15% PROTEIN L4 (L1). Q969Z9 Q4VBRO 32722 SMS: (SMS) SPERMINE SYNTHASE (EC PS2788 OOOS44 NM OO4595 1.05.15% 2.5.1.22) (SPERMIDINE Q9UQS1 AMINOPROPYLTRANSFERASE) (SPMSY). 32725 ZNF117 HUMAN: (ZNF117)ZINC FINGER Q03924 NM O15852 PROTEIN 117 (ZINC FINGER PROTEIN HPF9). 32726 ZNF2S7-ZNF92-ZNF43-ZNF273- Q9Y2O1 NM OO3423 ZNF680 HUMAN: (ZNF257 OR BMZF4)ZINC Q96HL5 NM 007139 FINGER PROTEIN 257 (BONE MARROW Q8NB35 NM 021148 ZINC FINGER4) (BMZF-4) (MGC12518) Q8N492 P17038 NM 033468 (FLJ34299) (ZNF43 ORZNF39 ORKOX27) Q8NEM1 NM 152626 ZINC FINGER PROTEIN 43 (ZINC PROTEIN P281 60 NM 178558 HTF6) (ZINC FINGER PROTEIN KOX27) Q96DG1 (ZNF273) (ZNF92) Q14593 Q

SEQUENCE LISTING

<16O NUMBER OF SEO ID NOS: 6

<210 SEQ ID NO 1 <211 LENGTH: 21 &212> TYPE: DNA <213> ORGANISM: Artificial sequence &220s FEATURE: <223> OTHER INFORMATION: DAZL primer <4 OO SEQUENCE: 1 ccaccacagt ttcagaatgt c 21

<210 SEQ ID NO 2 <211 LENGTH: 23 &212> TYPE: DNA <213> ORGANISM: Artificial sequence &220s FEATURE: <223> OTHER INFORMATION: DAZL primer <4 OO SEQUENCE: 2 caaagtttga gtgttgattta cca 23

<210 SEQ ID NO 3 <211 LENGTH: 21 &212> TYPE: DNA <213> ORGANISM: Artificial sequence &220s FEATURE: &223> OTHER INFORMATION: Oct-4 Primer

<4 OO SEQUENCE: 3 gaggaagctg acaacaatga a 21

<210 SEQ ID NO 4 <211 LENGTH: 21 US 2008/O 159999 A1 Jul. 3, 2008

- Continued

&212> TYPE: DNA <213> ORGANISM: Artificial sequence &220s FEATURE: &223> OTHER INFORMATION: Oct-4 Primer

<4 OO SEQUENCE: 4 ggttitt ctitt coctagotcc t 21

<210 SEQ ID NO 5 <211 LENGTH: 21 &212> TYPE: DNA <213> ORGANISM: Artificial sequence &220s FEATURE: &223> OTHER INFORMATION: Oct-4 Primer

<4 OO SEQUENCE: 5

Caggagat at gcaaagcaga a 21

<210 SEQ ID NO 6 <211 LENGTH: 2O &212> TYPE: DNA <213> ORGANISM: Artificial sequence &220s FEATURE: &223> OTHER INFORMATION: Oct-4 Primer

<4 OO SEQUENCE: 6 agcct caaaa toctict cott

What is claimed is: 10. A method for isolating germline-like stem cells from 1. An amniotic fluid cell composition comprising: amniotic fluid, said method comprising: (a) providing amniotic fluid cells on a Substrate for a Suf pluripotent embryonic stem cells expressing DAZL, and ficient time to permit a portion of said amniotic fluid amniotic fluid. cells to adhere to said substrate; 2. The composition of claim 1, wherein said amniotic fluid, (b) removing a non-adherent portion of said amniotic fluid comprises 5-50% of said basal growth medium. cells; 3. The composition of claim 1 wherein said stem cells may (c) identifying from said non-adherent portion of amniotic further express at least one marker selected from alkaline fluid cells, those cells expressing at least one germline phosphatase; SSEA-3; SSEA-4; TRA-1-60; TRA-1-81: like stem marker, said at least one germline-like stem TRA2-54; c-kit; Oct-4 and oxytocin receptor. marker being DAZL. 11. The method of claim 10, wherein said identifying step 4. The composition of claim 1 wherein said germline-like comprises performing flow cytometry analysis, immunocy stem cells may further express at least one of HLA Class I, tochemical analysis, or RT-PCR or a combination thereof. CD13, CD44, CD49b, and CD105. 12. A cell line isolated by method of claim 10. 5. The composition of claim 1 wherein said germline-like 13. The method of claim 10 wherein said germline-like stem cells may further express at least one of POU5F1, stem cells may further express at least one of alkaline phos TDGF, GABRB3, FGF4 and TERT. phatase; SSEA-3; SSEA-4; TRA-1-60; TRA-1-81: TRA2 6. The composition of claim 1 wherein said composition 54; c-kit; Oct-4 and oxytocin receptor. further comprises an agent selected from the group consisting 14. The method of claim 10 wherein said germline-like of forskolin (3R-(3a, 4C.f3, 5B, 6B, 6ao, 10C., 10C.f3, 10bc.)- stem cells do not express SSEA-1. 5-(acetyloxy)-3-ethenyldodecahydro-6,10,10b-trihydroxy 15. The method of claim 10 wherein said germline-like 3.4a, 7.7.10a-pentamethyl-1H-naphtho2.1-bipyran-1-one), stem cells may further express at least one of HLA Class I, cholera toxin, isobutylmethylxanthine (IBMX), and dibutyr CD13, CD44, CD49b, and CD105. ladenosine cyclic monophosphate (dbcAMP). 16. The method of claim 10 wherein said germline-like 7. The composition of claim 1, wherein said growth factor stem cells may further express at least one of POU5F1, is basic fibroblast growth factor (bfGF). TDGF, GABRB3, FGF4 and TERT. 8. The composition of claim 7 wherein the concentration of 17. An isolated amniotic fluid germline-like stem cell said bFGF is in the range of about 1-10 ng/ml. which is pluripotent and DAZL positive. 9. The composition of claim 1, wherein said basal growth 18. The isolated germline-like stem cell of claim 17 medium comprises one or more of L-glutamine, essential wherein said cell further expresses at least one of alkaline amino acids, non-essential amino acids, antibiotics and com phosphatase; SSEA-3; SSEA-4; TRA-1-60; TRA-1-81: binations thereof. TRA2-54; c-kit; Oct-4 and oxytocin receptor. US 2008/O 159999 A1 Jul. 3, 2008 74

19. The isolated germline-like stem cell as in claim 18 stroke, burns, heart disease, certain types of cancer, osteoar wherein said germline-like stem cells do not express SSEA-1. thritis, rheumatoid arthritis, leukemia, lymphoma, genetic 20. The isolated germline-like stem cell as in claim 19 blood disorders, and Alzheimer's disease. wherein said cell further expresses at least one of HLA Class 24. A culture medium for the growth of germline-like stem cells isolated from amniotic fluid, said culture medium com I, CD13, CD44, CD49b, and CD105. prising aminotic fluid and basal medium, said basal medium 21. The isolated germline-like stem cell as in claim 17 comprising: about 80% Dulbeco's modified Eagle's medium; wherein said cell further expresses at least one of POU5F1, and serum replacement medium. TDGF, GABRB3, FGF4 and TERT. 25. A culture medium of claim 24, further comprising one 22. A method of treating a disease in a human comprising of more of L-glutamine, nonessential amino acids, antibiot administering the cell or a plurality of said cell of claim 17 ics, a growth factor and other agent. into an individual in need thereof. 26. The culture medium of claim 24, wherein said growth 23. The method of claim 22 wherein said disease is selected factor is basic fibroblast growth factor (bFGF). from the group consisting of infertility, cirrhosis of the liver, pancreatitis, diabetes, Parkinson's disease, spinal cord injury, c c c c c