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Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State

2015-07Journal article Open access
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dc.contributor.authorPells, Steve
dc.contributor.authorKoutsouraki, Eirini
dc.contributor.authorMorfopoulou, Sofia
dc.contributor.authorValencia-Cadavid, Sara
dc.contributor.authorTomlinson, Simon R.
dc.contributor.authorKalathur, Ravi Kiran Reddy
dc.contributor.authorFutschik, Matthias E.
dc.contributor.authorDe Sousa, Paul A.
dc.date.accessioned2018-12-07T14:53:17Z
dc.date.available2018-12-07T14:53:17Z
dc.date.issued2015-07
dc.description.abstractHuman 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.description.sponsorshipEUFP7; Portuguese FCT [PTDC/BIA-GEN/116519/2010]; ESNATS (Embryonic Stem Cell Novel Alternative Testing Strategies) [FP7-201619]; Medical Research Council [G0300484]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1371/journal.pone.0131102
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11442
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library of Science
dc.relationAlternative splicing and its impact on molecular networks during stem cell differentiation
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDna Methylation
dc.subjectTranscription factor
dc.subjectEpigenetic signature
dc.subjectGene-expression
dc.subjectSomatic-cells
dc.subjectHuman Es
dc.subjectCulture
dc.subjectDifferentiation
dc.subjectLines
dc.subjectPluripotency
dc.titleNovel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlternative splicing and its impact on molecular networks during stem cell differentiation
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-GEN%2F116519%2F2010/PT
oaire.citation.issue7
oaire.citation.startPagee0131102
oaire.citation.titlePLoS ONE
oaire.citation.volume10
oaire.fundingStream3599-PPCDT
person.familyNameKalathur
person.familyNameFutschik
person.givenNameRavi Kiran Reddy
person.givenNameMatthias
person.identifier.ciencia-idA71B-AD01-3501
person.identifier.orcid0000-0003-2894-3345
person.identifier.orcid0000-0002-6245-8071
person.identifier.scopus-author-id22940879800
person.identifier.scopus-author-id14017989400
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication029974a3-d5b1-48f5-a44c-ca866e556336
relation.isAuthorOfPublicationd58f3269-c7e1-4c22-b094-5cfe6750821b
relation.isAuthorOfPublication.latestForDiscoveryd58f3269-c7e1-4c22-b094-5cfe6750821b
relation.isProjectOfPublicationbc3408f5-1888-4a55-aafb-6fbdbf9de224
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