Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
dc.contributor.author | Pells, S | |
dc.contributor.author | Koutsouraki, E | |
dc.contributor.author | Morfopoulou, S | |
dc.contributor.author | Valencia-Cadavid, S | |
dc.contributor.author | Tomlinson, SR | |
dc.contributor.author | Kalathur, R | |
dc.contributor.author | Futschik, Matthias | |
dc.contributor.author | De Sousa, PA | |
dc.date.accessioned | 2017-02-07T20:09:12Z | |
dc.date.available | 2017-02-07T20:09:12Z | |
dc.date.issued | 2015-07-07 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | ARTN e0131102 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/8418 | |
dc.description.abstract |
Human embryonic stem cells (hESCs) undergo epigenetic changes in vitro which may compromise function, so an epigenetic pluripotency "signature" would be invaluable for line validation. We assessed Cytosine-phosphate-Guanine Island (CGI) methylation in hESCs by genomic DNA hybridisation to a CGI array, and saw substantial variation in CGI methylation between lines. Comparison of hESC CGI methylation profiles to corresponding somatic tissue data and hESC mRNA expression profiles identified a conserved hESC-specific methylation pattern associated with expressed genes. Transcriptional repressors and activators were over-represented amongst genes whose associated CGIs were methylated or unmethylated specifically in hESCs, respectively. Knockdown of candidate transcriptional regulators (HMGA1, GLIS2, PFDN5) induced differentiation in hESCs, whereas ectopic expression in fibroblasts modulated iPSC colony formation. Chromatin immunoprecipitation confirmed interaction between the candidates and the core pluripotency transcription factor network. We thus identify novel pluripotency genes on the basis of a conserved and distinct epigenetic configuration in human stem cells. | |
dc.format.extent | e0131102-e0131102 | |
dc.format.medium | Electronic-eCollection | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Public Library of Science (PLoS) | |
dc.subject | Cell Differentiation | |
dc.subject | Cell Line | |
dc.subject | Cells, Cultured | |
dc.subject | CpG Islands | |
dc.subject | DNA Methylation | |
dc.subject | Epigenesis, Genetic | |
dc.subject | Epigenomics | |
dc.subject | Female | |
dc.subject | Fibroblasts | |
dc.subject | Gene Expression Profiling | |
dc.subject | Gene Regulatory Networks | |
dc.subject | HMGA1a Protein | |
dc.subject | Human Embryonic Stem Cells | |
dc.subject | Humans | |
dc.subject | Induced Pluripotent Stem Cells | |
dc.subject | Kruppel-Like Transcription Factors | |
dc.subject | Male | |
dc.subject | Protein Binding | |
dc.subject | RNA Interference | |
dc.subject | Repressor Proteins | |
dc.title | Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000358158900017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 7 | |
plymouth.volume | 10 | |
plymouth.publication-status | Published online | |
plymouth.journal | PLOS ONE | |
dc.identifier.doi | 10.1371/journal.pone.0131102 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Users by role | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2015-05-27 | |
dc.identifier.eissn | 1932-6203 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1371/journal.pone.0131102 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2015 | |
rioxxterms.type | Journal Article/Review |