38 Embryonic Stem Cell Research Literatures Mark Herbert, Phd

Total Page:16

File Type:pdf, Size:1020Kb

38 Embryonic Stem Cell Research Literatures Mark Herbert, Phd Embryonic Stem Cell Research Literatures Mark Herbert, PhD World Development Institute 39 Main Street, Flushing, Queens, New York 11354, USA, [email protected] Abstract: Stem cells are derived from embryonic and non-embryonic tissues. Most stem cell studies are for animal stem cells and plants have also stem cell. Stem cells were discovered in 1981 from early mouse embryos. Stem cells have the potential to develop into all different cell types in the living body. Stem cell is a body repair system. When a stem cell divides it can be still a stem cell or become adult cell, such as a brain cell. Stem cells are unspecialized cells and can renew themselves by cell division, and stem cells can also differentiate to adult cells with special functions. Stem cells replace the old cells and repair the damaged tissues. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin. This article introduces recent research reports as references in the related studies. [Mark H. Embryonic Stem Cell Research Literatures. Stem Cell 2019;10(4):38-217]. ISSN: 1945-4570 (print); ISSN: 1945-4732 (online). http://www.sciencepub.net/stem. 6. doi:10.7537/marsscj100419.06. Key words: stem cell; life; research; literature Introduction systems: suspension vs. adherent conditions. In the The stem cell is the origin of an organism’s life present study, an ES cell line derived from an Atoh1- that has the potential to develop into many different green fluorescent protein (GFP) transgenic mouse was types of cells in life bodies. In many tissues stem cells used to track the generation of otic progenitors, initial serve as a sort of internal repair system, dividing HCs and to compare these two differentiation systems. essentially without limit to replenish other cells as We used a two-step short-term differentiation method long as the person or animal is still alive. When a stem involving an induction period of 5 days during which cell divides, each new cell has the potential either to ES cells were cultured in the presence of remain a stem cell or become another type of cell with Wnt/transforming growth factor TGF-beta inhibitors a more specialized function, such as a red blood cell or and insulin-like growth factor IGF-1 to suppress a brain cell. This article introduces recent research mesoderm and reinforce presumptive ectoderm and reports as references in the related studies. otic lineages. The generated embryoid bodies were The following introduces recent reports as then differentiated in medium containing basic references in the related studies. fibroblast growth factor (bFGF) for an additional 5 days using either suspension or adherent culture Abboud, N., et al. (2017). "Culture conditions methods. Upon completion of differentiation, have an impact on the maturation of traceable, quantitative polymerase chain reaction analysis and transplantable mouse embryonic stem cell-derived otic immunostaining monitored the expression of otic/HC progenitor cells." J Tissue Eng Regen Med 11(9): progenitor lineage markers. The results indicate that 2629-2642. cells differentiated in suspension cultures produced The generation of replacement inner ear hair cells cells expressing otic progenitor/HC markers at a (HCs) remains a challenge and stem cell therapy holds higher efficiency compared with the production of the potential for developing therapeutic solutions to these cell types within adherent cultures. Furthermore, hearing and balance disorders. Recent developments we demonstrated that a fraction of these cells can have made significant strides in producing mouse otic incorporate into ototoxin-injured mouse postnatal progenitors using cell culture techniques to initiate HC cochlea explants and express MYO7A after differentiation. However, no consensus has been transplantation. Copyright (c) 2016 John Wiley & reached as to efficiency and therefore current methods Sons, Ltd. remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors Abd Jalil, A., et al. (2017). "Vitamin E-Mediated from embryonic stem (ES) cells in two cell culture Modulation of Glutamate Receptor Expression in an 38 Stem Cell 2019;10(4) http://www.sciencepub.net/stem SCJ Oxidative Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures." Evid Based Abdelbaset-Ismail, A., et al. (2016). "Vitamin D3 Complement Alternat Med 2017: 6048936. stimulates embryonic stem cells but inhibits migration Glutamate is the primary excitatory and growth of ovarian cancer and teratocarcinoma cell neurotransmitter in the central nervous system. lines." J Ovarian Res 9: 26. Excessive concentrations of glutamate in the brain can BACKGROUND: Deficiency in Vitamin D3 be excitotoxic and cause oxidative stress, which is (cholecalciferol) may predispose to some malignancies, associated with Alzheimer's disease. In the present including gonadal tumors and in experimental models study, the effects of vitamin E in the form of vitamin D3 has been proven to inhibit the growth of tocotrienol-rich fraction (TRF) and alpha-tocopherol cancer cells. To learn more about the potential role of (alpha-TCP) in modulating the glutamate receptor and vitamin D3 in cancerogenesis, we evaluated the neuron injury markers in an in vitro model of oxidative expression and functionality of the vitamin D receptor stress in neural-derived embryonic stem (ES) cell (VDR) and its role in metastasis of ovarian cancer cultures were elucidated. A transgenic mouse ES cell cells and of murine and human teratocarcinoma cell line (46C) was differentiated into a neural lineage in lines. METHODS: In our studies we employed murine vitro via induction with retinoic acid. These cells were embrynic stem cells (ESD3), murine (P19) and human then subjected to oxidative stress with a significantly (NTERA-2) teratocarcimona cells lines, human high concentration of glutamate. Measurement of ovarian cancer cells (A2780) as well as purified reactive oxygen species (ROS) was performed after murine and human purified very small embryonic like inducing glutamate excitotoxicity, and recovery from stem cells (VSELs). We evaluated expression of this toxicity in response to vitamin E was determined. Vitamin D3 receptor (VDR) in these cells as well as The gene expression levels of glutamate receptors and effect of vitamin D3 exposure on cell proliferation and neuron-specific enolase were elucidated using real- migration. RESULTS: We here provide also more time PCR. The results reveal that neural cells derived evidence for the role of vitamin D3 in germline- from 46C cells and subjected to oxidative stress derived malignancies, and this evidence supports the exhibit downregulation of NMDA, kainate receptor, proposal that vitamin D3 treatment inhibits growth and and NSE after posttreatment with different metastatic potential of several germline-derived concentrations of TRF and alpha-TCP, a sign of malignancies. We also found that the ESD3 murine neurorecovery. Treatment of either TRF or alpha-TCP immortalized embryonic stem cell line and normal, reduced the levels of ROS in neural cells subjected to pluripotent, germline-marker-positive very small glutamate-induced oxidative stress; these results embryonic-like stem cells (VSELs) isolated from adult indicated that vitamin E is a potent antioxidant. tissues are stimulated by vitamin D3, which suggests that vitamin D3 affects the earliest stages of Abdelalim, E. M. (2013). "Molecular embryogenesis. CONCLUSIONS: We found that mechanisms controlling the cell cycle in embryonic however all normal and malignant germ-line derived stem cells." Stem Cell Rev 9(6): 764-773. cells express functional VDR, Vitamin D3 differently Embryonic stem (ES) cells are originated from affects their proliferation and migration. We postulate the inner cell mass of a blastocyst stage embryo. They that while Vitamin D3 as anticancer drug inhibits can proliferate indefinitely, maintain an proliferation of malignant cells, it may protect normal undifferentiated state (self-renewal), and differentiate stem cells that play an important role in development into any cell type (pluripotency). ES cells have an and tissue/organ regeneration. unusual cell cycle structure, consists mainly of S phase cells, a short G1 phase and absence of G1/S Abdelhady, S., et al. (2013). "Erg channel is checkpoint. Cell division and cell cycle progression critical in controlling cell volume during cell cycle in are controlled by mechanisms ensuring the accurate embryonic stem cells." PLoS One 8(8): e72409. transmission of genetic information from generation to The cell cycle progression in mouse embryonic generation. Therefore, control of cell cycle is a stem cells (mESCs) is controlled by ion fluxes that complicated process, involving several signaling alter cell volume [1]. This suggests that ion fluxes pathways. Although great progress has been made on might control dynamic changes in morphology over the molecular mechanisms involved in the regulation the cell cycle, such as rounding up of the cell at of ES cell cycle, many regulatory mechanisms remain mitosis. However, specific channels regulating such unknown. This review summarizes the current dynamic changes and the possible interactions with knowledge about the molecular mechanisms regulating actomyosin complex have not been clearly identified. the cell cycle of ES cells and describes the relationship Following RNAseq
Recommended publications
  • STAT3-Ser/Hes3 Signaling: a New Molecular Component of the Neuroendocrine System?
    Review 77 STAT3-Ser/Hes3 Signaling: A New Molecular Component of the Neuroendocrine System? Authors P. Nikolakopoulou1, S. W. Poser1, J. Masjkur1, M. Fernandez Rubin de Celis1, L. Toutouna1, C. L. Andoniadou2, R. D. McKay3, G. Chrousos4, M. Ehrhart-Bornstein1, S. R. Bornstein1, A. Androutsellis-Theotokis1, 5, 6 Affiliations Affiliation addresses are listed at the end of the article Key words Abstract evidence suggests that a common non-canonical ●▶ STAT3 ▼ signaling pathway regulates adult progenitors in ●▶ Hes3 The endocrine system involves communication several different tissues, rendering it as a poten- ▶ stem cells ● among different tissues in distinct organs, includ- tially valuable starting point to explore their ing the pancreas and components of the Hypo- biology. The STAT3-Ser/Hes3 Signaling Axis was thalamic-Pituitary-Adrenal Axis. The molecular first identified as a major regulator of neural mechanisms underlying these complex interac- stem cells and, subsequently, cancer stem cells. In tions are a subject of intense study as they may the endocrine/neuroendocrine system, this path- hold clues for the progression and treatment of a way operates on several levels, regulating other variety of metabolic and degenerative diseases. A types of plastic cells: (a) it regulates pancreatic plethora of signaling pathways, activated by hor- islet cell function and insulin release; (b) insulin mones and other endocrine factors have been in turn activates the pathway in broadly distrib- implicated in this communication. Recent uted neural progenitors and possibly also hypo- advances in the stem cell field introduce a new thalamic tanycytes, cells with important roles in level of complexity: adult progenitor cells appear the control of the adrenal gland; (c) adrenal pro- to utilize distinct signaling pathways than the genitors themselves operate this pathway.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Supplemental Materials ZNF281 Enhances Cardiac Reprogramming
    Supplemental Materials ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E. Dickson, Kunhua Song, Wenduo Ye, Min S. Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A. Posner, Rhonda Bassel-Duby and Eric N. Olson Supplemental Table 1; related to Figure 1. Supplemental Table 2; related to Figure 1. Supplemental Table 3; related to the “quantitative mRNA measurement” in Materials and Methods section. Supplemental Table 4; related to the “ChIP-seq, gene ontology and pathway analysis” and “RNA-seq” and gene ontology analysis” in Materials and Methods section. Supplemental Figure S1; related to Figure 1. Supplemental Figure S2; related to Figure 2. Supplemental Figure S3; related to Figure 3. Supplemental Figure S4; related to Figure 4. Supplemental Figure S5; related to Figure 6. Supplemental Table S1. Genes included in human retroviral ORF cDNA library. Gene Gene Gene Gene Gene Gene Gene Gene Symbol Symbol Symbol Symbol Symbol Symbol Symbol Symbol AATF BMP8A CEBPE CTNNB1 ESR2 GDF3 HOXA5 IL17D ADIPOQ BRPF1 CEBPG CUX1 ESRRA GDF6 HOXA6 IL17F ADNP BRPF3 CERS1 CX3CL1 ETS1 GIN1 HOXA7 IL18 AEBP1 BUD31 CERS2 CXCL10 ETS2 GLIS3 HOXB1 IL19 AFF4 C17ORF77 CERS4 CXCL11 ETV3 GMEB1 HOXB13 IL1A AHR C1QTNF4 CFL2 CXCL12 ETV7 GPBP1 HOXB5 IL1B AIMP1 C21ORF66 CHIA CXCL13 FAM3B GPER HOXB6 IL1F3 ALS2CR8 CBFA2T2 CIR1 CXCL14 FAM3D GPI HOXB7 IL1F5 ALX1 CBFA2T3 CITED1 CXCL16 FASLG GREM1 HOXB9 IL1F6 ARGFX CBFB CITED2 CXCL3 FBLN1 GREM2 HOXC4 IL1F7
    [Show full text]
  • Supplemental Table 1. Complete Gene Lists and GO Terms from Figure 3C
    Supplemental Table 1. Complete gene lists and GO terms from Figure 3C. Path 1 Genes: RP11-34P13.15, RP4-758J18.10, VWA1, CHD5, AZIN2, FOXO6, RP11-403I13.8, ARHGAP30, RGS4, LRRN2, RASSF5, SERTAD4, GJC2, RHOU, REEP1, FOXI3, SH3RF3, COL4A4, ZDHHC23, FGFR3, PPP2R2C, CTD-2031P19.4, RNF182, GRM4, PRR15, DGKI, CHMP4C, CALB1, SPAG1, KLF4, ENG, RET, GDF10, ADAMTS14, SPOCK2, MBL1P, ADAM8, LRP4-AS1, CARNS1, DGAT2, CRYAB, AP000783.1, OPCML, PLEKHG6, GDF3, EMP1, RASSF9, FAM101A, STON2, GREM1, ACTC1, CORO2B, FURIN, WFIKKN1, BAIAP3, TMC5, HS3ST4, ZFHX3, NLRP1, RASD1, CACNG4, EMILIN2, L3MBTL4, KLHL14, HMSD, RP11-849I19.1, SALL3, GADD45B, KANK3, CTC- 526N19.1, ZNF888, MMP9, BMP7, PIK3IP1, MCHR1, SYTL5, CAMK2N1, PINK1, ID3, PTPRU, MANEAL, MCOLN3, LRRC8C, NTNG1, KCNC4, RP11, 430C7.5, C1orf95, ID2-AS1, ID2, GDF7, KCNG3, RGPD8, PSD4, CCDC74B, BMPR2, KAT2B, LINC00693, ZNF654, FILIP1L, SH3TC1, CPEB2, NPFFR2, TRPC3, RP11-752L20.3, FAM198B, TLL1, CDH9, PDZD2, CHSY3, GALNT10, FOXQ1, ATXN1, ID4, COL11A2, CNR1, GTF2IP4, FZD1, PAX5, RP11-35N6.1, UNC5B, NKX1-2, FAM196A, EBF3, PRRG4, LRP4, SYT7, PLBD1, GRASP, ALX1, HIP1R, LPAR6, SLITRK6, C16orf89, RP11-491F9.1, MMP2, B3GNT9, NXPH3, TNRC6C-AS1, LDLRAD4, NOL4, SMAD7, HCN2, PDE4A, KANK2, SAMD1, EXOC3L2, IL11, EMILIN3, KCNB1, DOK5, EEF1A2, A4GALT, ADGRG2, ELF4, ABCD1 Term Count % PValue Genes regulation of pathway-restricted GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, SMAD protein phosphorylation 9 6.34 1.31E-08 ENG pathway-restricted SMAD protein GDF3, SMAD7, GDF7, BMPR2, GDF10, GREM1, BMP7, LDLRAD4, phosphorylation
    [Show full text]
  • Genome-Wide DNA Methylation Analysis of KRAS Mutant Cell Lines Ben Yi Tew1,5, Joel K
    www.nature.com/scientificreports OPEN Genome-wide DNA methylation analysis of KRAS mutant cell lines Ben Yi Tew1,5, Joel K. Durand2,5, Kirsten L. Bryant2, Tikvah K. Hayes2, Sen Peng3, Nhan L. Tran4, Gerald C. Gooden1, David N. Buckley1, Channing J. Der2, Albert S. Baldwin2 ✉ & Bodour Salhia1 ✉ Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 diferentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in diferentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream efector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer. Activating KRAS mutations can be found in nearly 25 percent of all cancers1.
    [Show full text]
  • SUPPLEMENTARY MATERIAL Bone Morphogenetic Protein 4 Promotes
    www.intjdevbiol.com doi: 10.1387/ijdb.160040mk SUPPLEMENTARY MATERIAL corresponding to: Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells SUMIYO MIMURA, MIKA SUGA, KAORI OKADA, MASAKI KINEHARA, HIROKI NIKAWA and MIHO K. FURUE* *Address correspondence to: Miho Kusuda Furue. Laboratory of Stem Cell Cultures, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan. Tel: 81-72-641-9819. Fax: 81-72-641-9812. E-mail: [email protected] Full text for this paper is available at: http://dx.doi.org/10.1387/ijdb.160040mk TABLE S1 PRIMER LIST FOR QRT-PCR Gene forward reverse AP2α AATTTCTCAACCGACAACATT ATCTGTTTTGTAGCCAGGAGC CDX2 CTGGAGCTGGAGAAGGAGTTTC ATTTTAACCTGCCTCTCAGAGAGC DLX1 AGTTTGCAGTTGCAGGCTTT CCCTGCTTCATCAGCTTCTT FOXD3 CAGCGGTTCGGCGGGAGG TGAGTGAGAGGTTGTGGCGGATG GAPDH CAAAGTTGTCATGGATGACC CCATGGAGAAGGCTGGGG MSX1 GGATCAGACTTCGGAGAGTGAACT GCCTTCCCTTTAACCCTCACA NANOG TGAACCTCAGCTACAAACAG TGGTGGTAGGAAGAGTAAAG OCT4 GACAGGGGGAGGGGAGGAGCTAGG CTTCCCTCCAACCAGTTGCCCCAAA PAX3 TTGCAATGGCCTCTCAC AGGGGAGAGCGCGTAATC PAX6 GTCCATCTTTGCTTGGGAAA TAGCCAGGTTGCGAAGAACT p75 TCATCCCTGTCTATTGCTCCA TGTTCTGCTTGCAGCTGTTC SOX9 AATGGAGCAGCGAAATCAAC CAGAGAGATTTAGCACACTGATC SOX10 GACCAGTACCCGCACCTG CGCTTGTCACTTTCGTTCAG Suppl. Fig. S1. Comparison of the gene expression profiles of the ES cells and the cells induced by NC and NC-B condition. Scatter plots compares the normalized expression of every gene on the array (refer to Table S3). The central line
    [Show full text]
  • Methylome and Transcriptome Maps of Human Visceral and Subcutaneous
    www.nature.com/scientificreports OPEN Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal Received: 9 April 2019 Accepted: 11 June 2019 key epigenetic diferences at Published: xx xx xxxx developmental genes Stephen T. Bradford1,2,3, Shalima S. Nair1,3, Aaron L. Statham1, Susan J. van Dijk2, Timothy J. Peters 1,3,4, Firoz Anwar 2, Hugh J. French 1, Julius Z. H. von Martels1, Brodie Sutclife2, Madhavi P. Maddugoda1, Michelle Peranec1, Hilal Varinli1,2,5, Rosanna Arnoldy1, Michael Buckley1,4, Jason P. Ross2, Elena Zotenko1,3, Jenny Z. Song1, Clare Stirzaker1,3, Denis C. Bauer2, Wenjia Qu1, Michael M. Swarbrick6, Helen L. Lutgers1,7, Reginald V. Lord8, Katherine Samaras9,10, Peter L. Molloy 2 & Susan J. Clark 1,3 Adipocytes support key metabolic and endocrine functions of adipose tissue. Lipid is stored in two major classes of depots, namely visceral adipose (VA) and subcutaneous adipose (SA) depots. Increased visceral adiposity is associated with adverse health outcomes, whereas the impact of SA tissue is relatively metabolically benign. The precise molecular features associated with the functional diferences between the adipose depots are still not well understood. Here, we characterised transcriptomes and methylomes of isolated adipocytes from matched SA and VA tissues of individuals with normal BMI to identify epigenetic diferences and their contribution to cell type and depot-specifc function. We found that DNA methylomes were notably distinct between diferent adipocyte depots and were associated with diferential gene expression within pathways fundamental to adipocyte function. Most striking diferential methylation was found at transcription factor and developmental genes. Our fndings highlight the importance of developmental origins in the function of diferent fat depots.
    [Show full text]
  • 1714 Gene Comprehensive Cancer Panel Enriched for Clinically Actionable Genes with Additional Biologically Relevant Genes 400-500X Average Coverage on Tumor
    xO GENE PANEL 1714 gene comprehensive cancer panel enriched for clinically actionable genes with additional biologically relevant genes 400-500x average coverage on tumor Genes A-C Genes D-F Genes G-I Genes J-L AATK ATAD2B BTG1 CDH7 CREM DACH1 EPHA1 FES G6PC3 HGF IL18RAP JADE1 LMO1 ABCA1 ATF1 BTG2 CDK1 CRHR1 DACH2 EPHA2 FEV G6PD HIF1A IL1R1 JAK1 LMO2 ABCB1 ATM BTG3 CDK10 CRK DAXX EPHA3 FGF1 GAB1 HIF1AN IL1R2 JAK2 LMO7 ABCB11 ATR BTK CDK11A CRKL DBH EPHA4 FGF10 GAB2 HIST1H1E IL1RAP JAK3 LMTK2 ABCB4 ATRX BTRC CDK11B CRLF2 DCC EPHA5 FGF11 GABPA HIST1H3B IL20RA JARID2 LMTK3 ABCC1 AURKA BUB1 CDK12 CRTC1 DCUN1D1 EPHA6 FGF12 GALNT12 HIST1H4E IL20RB JAZF1 LPHN2 ABCC2 AURKB BUB1B CDK13 CRTC2 DCUN1D2 EPHA7 FGF13 GATA1 HLA-A IL21R JMJD1C LPHN3 ABCG1 AURKC BUB3 CDK14 CRTC3 DDB2 EPHA8 FGF14 GATA2 HLA-B IL22RA1 JMJD4 LPP ABCG2 AXIN1 C11orf30 CDK15 CSF1 DDIT3 EPHB1 FGF16 GATA3 HLF IL22RA2 JMJD6 LRP1B ABI1 AXIN2 CACNA1C CDK16 CSF1R DDR1 EPHB2 FGF17 GATA5 HLTF IL23R JMJD7 LRP5 ABL1 AXL CACNA1S CDK17 CSF2RA DDR2 EPHB3 FGF18 GATA6 HMGA1 IL2RA JMJD8 LRP6 ABL2 B2M CACNB2 CDK18 CSF2RB DDX3X EPHB4 FGF19 GDNF HMGA2 IL2RB JUN LRRK2 ACE BABAM1 CADM2 CDK19 CSF3R DDX5 EPHB6 FGF2 GFI1 HMGCR IL2RG JUNB LSM1 ACSL6 BACH1 CALR CDK2 CSK DDX6 EPOR FGF20 GFI1B HNF1A IL3 JUND LTK ACTA2 BACH2 CAMTA1 CDK20 CSNK1D DEK ERBB2 FGF21 GFRA4 HNF1B IL3RA JUP LYL1 ACTC1 BAG4 CAPRIN2 CDK3 CSNK1E DHFR ERBB3 FGF22 GGCX HNRNPA3 IL4R KAT2A LYN ACVR1 BAI3 CARD10 CDK4 CTCF DHH ERBB4 FGF23 GHR HOXA10 IL5RA KAT2B LZTR1 ACVR1B BAP1 CARD11 CDK5 CTCFL DIAPH1 ERCC1 FGF3 GID4 HOXA11 IL6R KAT5 ACVR2A
    [Show full text]
  • HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy
    cells Review HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy Carla De Giovanni 1,* , Lorena Landuzzi 2,†, Arianna Palladini 1 , Giordano Nicoletti 2, Patrizia Nanni 1 and Pier-Luigi Lollini 1,* 1 Laboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy; [email protected] (A.P.); [email protected] (P.N.) 2 Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy; [email protected] (L.L.); [email protected] (G.N.) * Correspondence: [email protected] (C.D.G.); [email protected] (P.-L.L.); Tel.: +39-051-2094786 (P.-L.L.) † Co-first author. Abstract: Rhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features allow for distinction between subtypes: morphology and presence/absence of a translocation be- tween the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation Citation: De Giovanni, C.; Landuzzi, with driving activity on tumor growth.
    [Show full text]
  • Single Cell Derived Clonal Analysis of Human Glioblastoma Links
    SUPPLEMENTARY INFORMATION: Single cell derived clonal analysis of human glioblastoma links functional and genomic heterogeneity ! Mona Meyer*, Jüri Reimand*, Xiaoyang Lan, Renee Head, Xueming Zhu, Michelle Kushida, Jane Bayani, Jessica C. Pressey, Anath Lionel, Ian D. Clarke, Michael Cusimano, Jeremy Squire, Stephen Scherer, Mark Bernstein, Melanie A. Woodin, Gary D. Bader**, and Peter B. Dirks**! ! * These authors contributed equally to this work.! ** Correspondence: [email protected] or [email protected]! ! Supplementary information - Meyer, Reimand et al. Supplementary methods" 4" Patient samples and fluorescence activated cell sorting (FACS)! 4! Differentiation! 4! Immunocytochemistry and EdU Imaging! 4! Proliferation! 5! Western blotting ! 5! Temozolomide treatment! 5! NCI drug library screen! 6! Orthotopic injections! 6! Immunohistochemistry on tumor sections! 6! Promoter methylation of MGMT! 6! Fluorescence in situ Hybridization (FISH)! 7! SNP6 microarray analysis and genome segmentation! 7! Calling copy number alterations! 8! Mapping altered genome segments to genes! 8! Recurrently altered genes with clonal variability! 9! Global analyses of copy number alterations! 9! Phylogenetic analysis of copy number alterations! 10! Microarray analysis! 10! Gene expression differences of TMZ resistant and sensitive clones of GBM-482! 10! Reverse transcription-PCR analyses! 11! Tumor subtype analysis of TMZ-sensitive and resistant clones! 11! Pathway analysis of gene expression in the TMZ-sensitive clone of GBM-482! 11! Supplementary figures and tables" 13" "2 Supplementary information - Meyer, Reimand et al. Table S1: Individual clones from all patient tumors are tumorigenic. ! 14! Fig. S1: clonal tumorigenicity.! 15! Fig. S2: clonal heterogeneity of EGFR and PTEN expression.! 20! Fig. S3: clonal heterogeneity of proliferation.! 21! Fig.
    [Show full text]
  • Projeto De Tese De Doutorado
    2 3 Agradecimentos Todo este trabalho não teria sido realizado se não fosse pelo apoio e credibilidade de pessoas importantes que fazem parte da minha vida, com as quais eu pude contar incondicionalmente. Agradeço ao Professor Hernandes F. Carvalho, por me orientar desde meu treinamento técnico, por acreditar na minha capacidade profissional, aceitando-me como sua aluna no Mestrado em Biologia Celular e por sempre ter me dado todo apoio intelectual e estrutural para prosseguir neste caminho. A todos os integrantes do Laboratório de Matriz Extracelular: Adauto, Augusto, Fabiana, Fiama, Guilherme, Gustavo, Juliete, Renan, Rony, Sílvia, Umar, por sempre dividirem comigo conhecimentos teóricos e práticos, felicidades e angústias. Em especial ao ex e aos ainda integrantes do laboratório: Alexandre, por ter me ensinado muitas das coisas que hoje sei e me aceitado como colaboradora em seus trabalhos; à Ana Milena pela dedicação e colaboração essencial na escrita dos manuscritos; ao Danilo, pela paciência e ajuda integral nos tratamentos dos animais; à Taize, pela permanente disposição em ajudar nos experimentos e acolhimento desde a minha chegada à UNICAMP. Ao Ramon Vidal Oliveira, do LNBio pela assistência e realização da análise de bioinformática dos dados obtidos na técnica de microarray. À Maria Eugênia Ribeiro Camargo, pela disponibilidade e auxílio na utilização do Laboratório de Microarray (LNBio). À Professora Maria Julia Marques, por ter nos cedido seu equipamento para a revelação das memebranas de Western Blotting. Em especial às suas alunas Samara, Cíntia, Ana Paula, Letícia, Adriane, Adriele pela disposição e ajuda sempre que precisei. 4 À Professora Heide Dolder, por ter seu laboratório de portas abertas para utilização dos micrótomos.
    [Show full text]
  • Pubertal Androgenization and Gonadal Histology in Two 46,XY
    European Journal of Endocrinology (2012) 166 341–349 ISSN 0804-4643 CASE REPORT Pubertal androgenization and gonadal histology in two 46,XY adolescents with NR5A1 mutations and predominantly female phenotype at birth M Cools1, P Hoebeke2, K P Wolffenbuttel3, H Stoop4, R Hersmus4, M Barbaro5, A Wedell5, H Bru¨ggenwirth6, L H J Looijenga4 and S L S Drop7 1Division of Pediatric Endocrinology, Department of Pediatrics, Division of Pediatric Urology, Department of Urology, University Hospital Ghent, Ghent University, Building 3K12D, De Pintelaan 185, 9000 Ghent, Belgium, 2University Hospital Ghent, Ghent University, Ghent, Belgium, 3Division of Pediatric Urology, Department of Urology, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands, 4Department of Pathology, Josephine Nefkens Institute, Daniel Den Hoed Cancer Center,Erasmus Medical Center,Rotterdam, The Netherlands, 5Department of Molecular Medicine and Surgery, Karolinska Institutet, Center for Inherited Metabolic Diseases (CMMS), Karolinska University Hospital, Stockholm, Sweden, 6Department of Clinical Genetics and 7Division of Pediatric Endocrinology, Department of Pediatrics, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands (Correspondence should be addressed to M Cools; Email: [email protected]) Abstract Objective: Most patients with NR5A1 (SF-1) mutations and poor virilization at birth are sex-assigned female and receive early gonadectomy. Although studies in pituitary-specific Sf-1 knockout mice suggest hypogonadotropic hypogonadism, little is known about endocrine function at puberty and on germ cell tumor risk in patients with SF-1 mutations. This study reports on the natural course during puberty and on gonadal histology in two adolescents with SF-1 mutations and predominantly female phenotype at birth.
    [Show full text]