DOCSLIB.ORG

Chromatin Signatures of Pluripotent Cell Lines

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chromatin Signatures of Pluripotent Cell Lines LETTERS Chromatin signatures of pluripotent cell lines Véronique Azuara 1,2,7, Pascale Perry1, Stephan Sauer1, Mikhail Spivakov1, Helle F. Jørgensen1, Rosalind M. John1,3, Mina Gouti1,4, Miguel Casanova5, Gary Warnes6, Matthias Merkenschlager1 and Amanda G. Fisher1,7 Epigenetic genome modifications are thought to be important (HSCs). Early replication during S phase is widely considered a feature for specifying the lineage and developmental stage of of gene-rich, transcriptionally active regions of the genome and cor- cells within a multicellular organism. Here, we show that relates with accessible chromatin carrying acetylated histones, whereas the epigenetic profile of pluripotent embryonic stem cells late replication is characteristic of constitutive heterochromatin and (ES) is distinct from that of embryonic carcinoma cells, some facultative heterochromatin15–17. The timing of DNA replication haematopoietic stem cells (HSC) and their differentiated of a panel of transcriptional regulatory genes (which are important for progeny. Silent, lineage-specific genes replicated earlier early development or for the specification of neural, haematopoietic in pluripotent cells than in tissue-specific stem cells or or muscle lineages) was compared in pluripotent ES cells, multipotent differentiated cells and had unexpectedly high levels of haematopoietic cell lines and unipotent T lymphocytes (Fig. 1 and see acetylated H3K9 and methylated H3K4. Unusually, in ES Supplementary Information, Fig. S1). Replication timing was assessed cells these markers of open chromatin were also combined using a previously described method16 in which cell populations are with H3K27 trimethylation at some non-expressed genes. pulse-labelled with 5-bromo-2′-deoxyuridine (BrdU), fractionated Thus, pluripotency of ES cells is characterized by a specific according to cell-cycle stage and the abundance of candidate sequences epigenetic profile where lineage-specific genes may be within newly synthesized DNA determined using semi-quantitative PCR accessible but, if so, carry repressive H3K27 trimethylation or real-time quantitative (q) PCR. This allows locus replication to be modifications. H3K27 methylation is functionally important for compared in different cell types without the need to synchronise cells. preventing expression of these genes in ES cells as premature Representative cell-cycle profiles of ES, HSC and T cells with appropriate expression occurs in embryonic ectoderm development (Eed)- early (α-globin) and late (Amylase 2–1 and X141) replicating controls16 deficient ES cells. Our data suggest that lineage-specific genes are shown in the Supplementary Information, Fig. S1a. Replication tim- are primed for expression in ES cells but are held in check by ing is shown as a gradation of colour from green (earliest) to red (latest; opposing chromatin modifications. Fig. 1a, b). The replication profiles for each of the three independently derived ES cell lines CCE, OSG and OS25, were remarkably similar. Most Transcriptional profiling of stem cells has allowed the identification of genes replicated within the first quarter (65%) or first half (90%) of S genes that are important for stem-cell biology1–3, but a lack of consensus phase, including Oct4, Rex1 and Nanog10,11 and genes that are expressed between data sets has called into question whether a common molecu- in blood or neural lineages (such as Ikaros and PU.1, Sox1 and neu- lar identity or ‘signature’ can be accurately defined4–6. Parallel studies rogenin, respectively) but not in ES cells. Some genes (Myf5, Neurod using epigenetic markers have suggested that epigenetic profiles may and Mash1) and constitutive heterochromatin (K-satellite and X141) be valuable indicators of cell identity7–13. ES cells, unlike tissue-specific consistently replicated late in ES cells, confirming that the analysis was stem-cell populations, have a broad range of lineage options, consistent not inadvertently skewed towards early replication. with their origin from pluripotential cells within the inner cell mass The replication profiles of two different sources of haematopoietic of the developing embryo14. Here, we examine whether ES cells have stem cells (the IL-3 dependent FDCP (factor-dependent cell-pater- epigenetic features that distinguish them from stem cells with more son)-mix A4 clone18 and Pax5-deficient progenitors19) and of T lym- restricted developmental potential, such as haematopoietic stem cells phocytes were distinct from ES cells. Although a substantial proportion 1Lymphocyte Development Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 2Current address: Stem Cell Initiative, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 3Current addres: Cardiff School of Biosciences, Cardiff CF10 3US, UK. 4Current address: Developmental Biology Laboratory, Foundation for Biomedical Research of the Academy of Athens, Soranou Ephessiou 4, Athens 11527, Greece. 5Developmental Epigenetics Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. 6FACS Laboratory, Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK. 7Correspondence should be addressed to V.A. or A.G.F. (e-mail: [email protected]; [email protected]) Received 22 November 2005; accepted 16 March 2006; published online 29 March 2006; DOI: 10/1038 ncb1403 532 NATURE CELL BIOLOGY VOLUME 8 | NUMBER 5 | MAY 2006 © 2006 Nature Publishing Group pprintrint nncb1403.inddcb1403.indd 553232 110/4/060/4/06 33:11:20:11:20 ppmm LETTERS ab ES HSC T CCE OSG OS25 A4Pax5−/− T G1 S1 S2 S3 S4 G2 Cripto E Esg1 Fgf4 ME Foxd3 Nanog M Oct4 Rex1 Utf1 ML C/EBPα c-myb L Ebf Gata1 Gata2 Gata3 Ikaros Lmo2 NF-E2 Pax5 PU.1 Scl c Rex1 Irx3 Math1 T-bet Myf5 G1 S1 S2 S3 S4 G2 G1 S1 S2 S3 S4 G2 G1 S1 S2 S3 S4 G2 MyoD ES Myog Hes1 T Hes5 Irx3 Mash1 Msx1 Nkx2−2 Nkx2−9 Math1 G1 S1 S2 S3 S4 G2 G1 S1 S2 S3 S4 G2 G1 S1 S2 S3 S4 G2 Msx1 ES Neurod Ngn1 T Ngn2 Nkx2−2 Nkx2−9 Pax3 Sox1 Sox2 Olig2 G1 S1 S2 S3 S4 G2 G1 S1 S2 S3 S4 G2 G1 S1 S2 S3 S4 G2 Pax3 ES Pax6 Pax7 T Sox1 Sox2 Sox3 Figure 1 Pluripotent ES cells, multipotent HSC and unipotent T lymphocytes (middle–late, ML) or S4–G2 (late, L), determined in at least two independent have distinct replication timing profiles. (a, b) The replication timing experiments. To facilitate a comparison between different cell types, comparisons of candidate genes between three embryonic stem cell lines replication timing assignments are represented in a gradation of colours from (CCE, OSG, and OS25), the FDCP-mix A4 clone and Pax5-deficient pro-B dark green (E), to light green (ME), to yellow (M), to orange (ML) to red (L) cells representing two populations of haematopoietic progenitors (HSC), as shown in b. Genes marked by asterisks consistently replicate later in HSC and primary T cells are shown (a). The replication timing of each gene and T cells than in ES cells. (c) Southern blot comparisons of the abundance was defined according to its peak abundance in G1–S1 phase (early, E), of PCR product for Rex1, Irx3, Math1, Msx1, Nkx2-2, Nkx2-9, Pax3, Sox1 S2 phase (middle–early, ME), S2 and S3 phase (middle, M), S3 phase and Sox2 loci in ES and T cell fractions. of genes replicated within the first quarter (42–47%) or half of S phase and P19, which share the expression of numerous markers with ES cells (69–76%), the proportion of late-replicating genes increased to approxi- but have a much narrower range of lineage potential, was examined20. mately 20% in these haematopoietic cells (Fig. 1a and see Supplementary Replication timing was different between the two embryonic carcinoma Information, Fig. S2). Loci that replicated later in HSC and T cells than in cell lines and distinct from that of ES cells (Fig. 2). Several neural genes ES cells (asterisked in Fig. 1a) could be divided into two groups. The first replicated slightly later in F9 cells than in ES cells. F9 cells have a propen- group, as exemplified by Rex1, is expressed early in embryonic develop- sity to differentiate towards endoderm lineages21. In contrast, a shift to ment and was previously shown to shift to later replication during ES cell earlier replication of several neural genes was seen in P19 cells, resulting differentiation and transcriptional shut down10,11. The second group is in a profile that was more similar to ES-derived neural precursors10. P19 comprised of a subset of neural-specific genes that are not thought to be cells preferentially differentiate towards neuronal lineages22. Therefore, expressed by ES cells, HSC or lymphocytes (Irx3, Math1, Msx1, Nkx2–2, the replication profiles observed reflect the different potentials of these Nkx2–9, Pax3 and Sox1), but are selectively replicated earlier in ES cells embryonic carcinoma cell lines. (which retain neural potential) than in haematopoietic cells (which have The later replication of several neural-specific genes in T cells than lost neural potential; Fig. 1c). This observation implies that these epige- in ES cells (Fig. 1) may indicate underlying differences in the chromatin netic changes may reflect differences in transcriptional ‘competence’ and structure. To investigate this possibility, chromatin immunoprecipitation lineage affiliation, rather than overt changes in gene transcription. analysis was performed using a panel of antibodies that
Load more

Recommended publications
  • Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells
    Table S1 The four gene sets derived from gene expression profiles of ESCs and differentiated cells Uniform High Uniform Low ES Up ES Down EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol 269261 Rpl12 11354 Abpa 68239 Krt42 15132 Hbb-bh1 67891 Rpl4 11537 Cfd 26380 Esrrb 15126 Hba-x 55949 Eef1b2 11698 Ambn 73703 Dppa2 15111 Hand2 18148 Npm1 11730 Ang3 67374 Jam2 65255 Asb4 67427 Rps20 11731 Ang2 22702 Zfp42 17292 Mesp1 15481 Hspa8 11807 Apoa2 58865 Tdh 19737 Rgs5 100041686 LOC100041686 11814 Apoc3 26388 Ifi202b 225518 Prdm6 11983 Atpif1 11945 Atp4b 11614 Nr0b1 20378 Frzb 19241 Tmsb4x 12007 Azgp1 76815 Calcoco2 12767 Cxcr4 20116 Rps8 12044 Bcl2a1a 219132 D14Ertd668e 103889 Hoxb2 20103 Rps5 12047 Bcl2a1d 381411 Gm1967 17701 Msx1 14694 Gnb2l1 12049 Bcl2l10 20899 Stra8 23796 Aplnr 19941 Rpl26 12096 Bglap1 78625 1700061G19Rik 12627 Cfc1 12070 Ngfrap1 12097 Bglap2 21816 Tgm1 12622 Cer1 19989 Rpl7 12267 C3ar1 67405 Nts 21385 Tbx2 19896 Rpl10a 12279 C9 435337 EG435337 56720 Tdo2 20044 Rps14 12391 Cav3 545913 Zscan4d 16869 Lhx1 19175 Psmb6 12409 Cbr2 244448 Triml1 22253 Unc5c 22627 Ywhae 12477 Ctla4 69134 2200001I15Rik 14174 Fgf3 19951 Rpl32 12523 Cd84 66065 Hsd17b14 16542 Kdr 66152 1110020P15Rik 12524 Cd86 81879 Tcfcp2l1 15122 Hba-a1 66489 Rpl35 12640 Cga 17907 Mylpf 15414 Hoxb6 15519 Hsp90aa1 12642 Ch25h 26424 Nr5a2 210530 Leprel1 66483 Rpl36al 12655 Chi3l3 83560 Tex14 12338 Capn6 27370 Rps26 12796 Camp 17450 Morc1 20671 Sox17 66576 Uqcrh 12869 Cox8b 79455 Pdcl2 20613 Snai1 22154 Tubb5 12959 Cryba4 231821 Centa1 17897
    [Show full text]
  • Cellular and Molecular Signatures in the Disease Tissue of Early
    Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of
    [Show full text]
  • Supplementary Materials
    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
    [Show full text]
  • The Epigenome in Pluripotency and Differentiation
    Review Review The epigenome in pluripotency and differentiation The ability to culture pluripotent stem cells and direct their differentiation into Rathi D Thiagarajan1, Robert specific cell types in vitro provides a valuable experimental system for modeling Morey1 & Louise C Laurent*1 1 pluripotency, development and cellular differentiation. High-throughput profiling of Department of Reproductive Medicine, The University of California, San Diego, the transcriptomes and epigenomes of pluripotent stem cells and their differentiated La Jolla, CA, USA derivatives has led to identification of patterns characteristic of each cell type, *Author for correspondence: discovery of new regulatory features in the epigenome and early insights into the [email protected] complexity of dynamic interactions among regulatory elements. This work has also revealed potential limitations of the use of pluripotent stem cells as in vitro models of developmental events, due to epigenetic variability among different pluripotent stem cell lines and epigenetic instability during derivation and culture, particularly at imprinted and X-inactivated loci. This review focuses on the two most well-studied epigenetic mechanisms, DNA methylation and histone modifications, within the context of pluripotency and differentiation. Keywords: differentiation • DNA methylation • epigenome • histone modification • imprinting • pluripotency • sequencing • stem cells • X inactivation Early mammalian development involves genetic mechanisms in the regulation of the precise orchestration
    [Show full text]
  • Altered DNA Methylation Pattern Characterizes the Peripheral Immune Cells of Patients with Autoimmune Hepatitis
    medRxiv preprint doi: https://doi.org/10.1101/2021.07.01.21259836; this version posted July 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis Kalliopi Zachou1,2*, Pinelopi Arvaniti1*, Aggeliki Lyberopoulou1, Eirini Sevdali3, Matthaios Speletas3, Maria Ioannou4, George K. Koukoulis4, Yves Renaudineau5,6**, George N. Dalekos1,2** *These authors contributed equally to this work **These authors contributed equally to this work as senior authors 1Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, Greece; 2Institute of Internal Medicine and Hepatology, 41447 Larissa, Greece; 3Department of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; 4Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; 5INSERN U1291, CNR U5051, University Toulouse III, Toulouse Institute for infectious and inflammatory diseases, Toulouse, France; 6Department of Immunology, Purpan University Hospital Toulouse, Toulouse, France All correspondence and reprint requests to: George N. Dalekos, MD, PhD Professor of Medicine Head, Department of Medicine and Research Laboratory of Internal Medicine National Expertise Center of Greece in Autoimmune Liver Diseases General University Hospital of Larissa, 41110 Larissa, Greece Tel: ++30-241-350-2285; Fax: ++30-241-350-1557 e-mail: [email protected] NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
    [Show full text]
  • ZFP57 Gene ZFP57 Zinc Finger Protein
    ZFP57 gene ZFP57 zinc finger protein Normal Function The protein produced from the ZFP57 gene is a member of a family called zinc finger proteins, which are involved in many cellular functions. Zinc finger proteins each contain one or more short regions called zinc finger domains. These regions include a specific pattern of protein building blocks (amino acids) and one or more charged atoms of zinc ( zinc ions). Zinc finger proteins attach (bind) primarily to DNA. In most cases, these proteins attach to regions near certain genes and turn the genes on and off as needed. Proteins that bind to DNA and regulate the activity of particular genes are known as transcription factors. Some zinc finger proteins can also bind to other molecules, including RNA (a chemical cousin of DNA) and proteins. The ZFP57 protein is involved in the regulation of other genes by the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms (methylation). Methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and lipids, and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). Health Conditions Related to Genetic Changes 6q24-related transient neonatal diabetes mellitus Mutations in the ZFP57 gene cause about 10 percent of cases of 6q24-related transient neonatal diabetes mellitus, a type of diabetes that occurs in infants. This disorder results from the overactivity (overexpression) of certain genes in a region of the long (q) arm of chromosome 6 called 6q24.
    [Show full text]
  • WO 2019/089592 Al 09 May 2019 (09.05.2019) W 1 P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization III International Bureau (10) International Publication Number (43) International Publication Date WO 2019/089592 Al 09 May 2019 (09.05.2019) W 1 P O PCT (51) International Patent Classification: (72) Inventors; and A61K 35/12 (2015.01) C07K 16/30 (2006.01) (71) Applicants: JAN, Max [US/US]; c/o The Broad Institute, A61K 5/7 7 (2015.01) C07K 14/705 (2006.01) Inc., 45 1 Main Street, Cambridge, Massachusetts 02142 (US). SIEVERS, Quinlan [US/US]; c/o The Broad In¬ (21) International Application Number: stitute, Inc., 451 Main Street, Cambridge, Massachusetts PCT/US2018/058210 02142 (US). EBERT, Benjamin [US/US]; c/o The Broad (22) International Filing Date: Institute, Inc., 451 Main Street, Cambridge, Massachusetts 30 October 2018 (30. 10.2018) 02142 (US). MAUS, Marcela [US/US]; c/o The Broad In¬ stitute, Inc., 451 Main Street, Cambridge, Massachusetts (25) Filing Language: English 02142 (US). (26) Publication Language: English (74) Agent: COWLES, Christopher R. et al; Burns & Levin- (30) Priority Data: son, LLP, 125 Summer Street, Boston, Massachusetts 62/579,454 3 1 October 2017 (3 1. 10.2017) U S 021 10 (US). 62/633,725 22 February 2018 (22.02.2018) U S (81) Designated States (unless otherwise indicated, for every (71) Applicants: THE GENERAL HOSPITAL CORPO¬ kind of national protection available): AE, AG, AL, AM, RATION [US/US]; 55 Fruit Street, Boston, Massachu¬ AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, setts 021 14 (US) BRIGHAM & WOMEN'S HOSPITAL CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, [US/US]; 75 Francis Street, Boston, Massachusetts 021 15 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (US) PRESIDENT AND FELLOWS OF HARVARD HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, COLLEGE [US/US]; 17 Quincy Street, Cambridge, Mass¬ KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, achusetts 02138 (US).
    [Show full text]
  • Supplementary Items
    Electronic Supplementary Material (ESI) for Molecular Omics. This journal is © The Royal Society of Chemistry 2019 Supplementary Items Mean expression (TPM) Log2 fold change Marker gene Cell type specificity control goblet Paneth goblet v ctrl Paneth v ctrl Lgr5 Stem 71.88 4.08 12.76 -2.77 -1.16 ChgA Enteroendocrine 56.49 507.58 287.2 2.42 2.17 Muc2 Goblet 47.26 625.05 185.18 2.81 1.83 Cd24a Paneth 471.23 1034.85 708.78 1.05 NA Lyz1 Paneth 2613.91 11576.37 22065.95 1.72 2.67 Vil1 Epithelial 211.13 219.22 89.02 NA NA Table S2: Expression and differential expression values for primary cell-type markers. Expression given as mean transcripts per million (TPM) for each enteroid type. Log2 fold changes values given where differential expression criteria passed (q value ≤ 0.05 and log2 fold change ≥ |1|). Control- normally differentiated enteroids; Paneth= Paneth cell enriched enteroids; goblet= goblet cell enriched enteroids. Paneth Paneth Goblet Goblet Gene Type Gene Name Ensembl ID DEG lfc DEG fdr DEG lfc DEG fdr AMP Ang4 ENSMUSG00000060615 4.64 8.61E-36 2.45 8.75E-13 AMP Defa17 ENSMUSG00000060208 4.02 6.40E-46 2.95 5.56E-31 AMP Defa2 ENSMUSG00000096295 4.58 1.70E-18 NA NA AMP Defa20 ENSMUSG00000095066 4.40 1.19E-17 NA NA AMP Defa21 ENSMUSG00000074447 5.18 2.22E-22 NA NA AMP Defa22 ENSMUSG00000074443 5.40 3.09E-20 NA NA AMP Defa23 ENSMUSG00000074446 3.69 1.94E-12 NA NA AMP Defa24 ENSMUSG00000064213 3.91 8.51E-38 3.24 1.92E-32 AMP Defa26 ENSMUSG00000060070 3.02 1.86E-39 2.22 8.61E-27 AMP Defa28 ENSMUSG00000074434 2.84 3.21E-17 1.66 1.20E-07
    [Show full text]
  • Stem Cell 2015;6(2) 56
    Stem Cell 2015;6(2) http://www.sciencepub.net/stem Stem Cell and Transcript Research Literatures Ma Hongbao 1, Margaret Young 2, Yang Yan 1 1 Brookdale Hospital, Brooklyn, New York 11212, USA; 2 Cambridge, MA 02138, USA [email protected] Abstract: The stem cell is the origin of an organism’s life that has the potential to develop into many different types of cells in life bodies. In many tissues stem cells serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a red blood cell or a brain cell. This article introduces recent research reports as references in the stem cell and transcript related studies. [Ma H, Young M, Yang Y. Stem Cell and Transcript Research Literatures. Stem Cell. 2015;6(2):56-72] (ISSN 1545-4570). http://www.sciencepub.net/stem. 8 Key words: stem cell; transcript; life; research; literature 1. Introduction REST (322) target genes. The majority of these The stem cell is the origin of an organism’s life CoREST targets do not contain known RE1 motifs. that has the potential to develop into many different Notably, these CoREST target genes do play important types of cells in life bodies. In many tissues stem cells roles in pluripotency networks, in modulating NSC serve as a sort of internal repair system, dividing identity and fate decisions and in epigenetic processes essentially without limit to replenish other cells as previously associated with both REST and CoREST.
    [Show full text]
  • WO 2012/054896 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number ι (43) International Publication Date ¾ ί t 2 6 April 2012 (26.04.2012) WO 2012/054896 Al (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, C12N 5/00 (2006.01) C12N 15/00 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, C12N 5/02 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (21) International Application Number: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, PCT/US201 1/057387 ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (22) International Filing Date: NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, 2 1 October 201 1 (21 .10.201 1) RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (25) Filing Language: English ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/406,064 22 October 2010 (22.10.2010) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 61/415,244 18 November 2010 (18.1 1.2010) US UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, (71) Applicant (for all designated States except US): BIO- DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, TIME INC.
    [Show full text]
  • Regulatory Network Analysis of Paneth Cell and Goblet Cell Enriched Gut Organoids Using Transcriptomics Approaches
    bioRxiv preprint doi: https://doi.org/10.1101/575845; this version posted October 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches Treveil A1,2*, Sudhakar P1,3*, Matthews Z J4*, Wrzesinski T1, Jones E J1,2, Brooks J1,2,4,5, Olbei M1,2, Hautefort I1, Hall L J2, Carding S R2,4, Mayer U6, Powell P P4, Wileman T2,4, Di Palma F1, Haerty W1,#, Korcsmáros T1,2# 1 Earlham Institute, Norwich Research Park, Norwich, Norfolk, NR4 7UZ, UK 2 Quadram Institute, Norwich Research Park, Norwich, Norfolk, NR4 7UA, UK 3 Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium 4 Norwich Medical School, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK 5 Department of Gastroenterology, Norfolk and Norwich University Hospitals, Norwich, UK 6 School of Biological Sciences, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK * Equal contributions # Joint corresponding authors Corresponding author contact details: Dr Tamas Korcsmaros ORCID id : https://orcid.org/0000-0003-1717-996X [email protected] Phone : 0044-1603450961 Fax : 0044-1603450021 Address: Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK 1 bioRxiv preprint doi: https://doi.org/10.1101/575845; this version posted October 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Identification of Biomarkers, Pathways and Potential Therapeutic Targets for Heart Failure Using Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2021.08.05.455244; this version posted August 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Identification of biomarkers, pathways and potential therapeutic targets for heart failure using bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karnataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2021.08.05.455244; this version posted August 6, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Heart failure (HF) is a complex cardiovascular diseases associated with high mortality. To discover key molecular changes in HF, we analyzed next-generation sequencing (NGS) data of HF. In this investigation, differentially expressed genes (DEGs) were analyzed using limma in R package from GSE161472 of the Gene Expression Omnibus (GEO). Then, gene enrichment analysis, protein-protein interaction (PPI) network, miRNA-hub gene regulatory network and TF-hub gene regulatory network construction, and topological analysis were performed on the DEGs by the Gene Ontology (GO), REACTOME pathway, STRING, HiPPIE, miRNet, NetworkAnalyst and Cytoscape. Finally, we performed receiver operating characteristic curve (ROC) analysis of hub genes. A total of 930 DEGs 9464 up regulated genes and 466 down regulated genes) were identified in HF.
    [Show full text]