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

Detalhes bibliográficos
Autor(a) principal: Pells, Steve
Data de Publicação: 2015
Outros Autores: Koutsouraki, Eirini, Morfopoulou, Sofia, Valencia-Cadavid, Sara, Tomlinson, Simon R., Kalathur, Ravi Kiran Reddy, Futschik, Matthias E., De Sousa, Paul A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/11442
Resumo: 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.
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spelling Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation StateDna MethylationTranscription factorEpigenetic signatureGene-expressionSomatic-cellsHuman EsCultureDifferentiationLinesPluripotencyHuman 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.EUFP7; Portuguese FCT [PTDC/BIA-GEN/116519/2010]; ESNATS (Embryonic Stem Cell Novel Alternative Testing Strategies) [FP7-201619]; Medical Research Council [G0300484]Public Library of ScienceSapientiaPells, SteveKoutsouraki, EiriniMorfopoulou, SofiaValencia-Cadavid, SaraTomlinson, Simon R.Kalathur, Ravi Kiran ReddyFutschik, Matthias E.De Sousa, Paul A.2018-12-07T14:53:17Z2015-072015-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11442eng1932-620310.1371/journal.pone.0131102info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:23:15Zoai:sapientia.ualg.pt:10400.1/11442Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:02:57.051551Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
title Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
spellingShingle Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
Pells, Steve
Dna Methylation
Transcription factor
Epigenetic signature
Gene-expression
Somatic-cells
Human Es
Culture
Differentiation
Lines
Pluripotency
title_short Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
title_full Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
title_fullStr Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
title_full_unstemmed Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
title_sort Novel Human Embryonic Stem Cell Regulators Identified by Conserved and Distinct CpG Island Methylation State
author Pells, Steve
author_facet Pells, Steve
Koutsouraki, Eirini
Morfopoulou, Sofia
Valencia-Cadavid, Sara
Tomlinson, Simon R.
Kalathur, Ravi Kiran Reddy
Futschik, Matthias E.
De Sousa, Paul A.
author_role author
author2 Koutsouraki, Eirini
Morfopoulou, Sofia
Valencia-Cadavid, Sara
Tomlinson, Simon R.
Kalathur, Ravi Kiran Reddy
Futschik, Matthias E.
De Sousa, Paul A.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv Pells, Steve
Koutsouraki, Eirini
Morfopoulou, Sofia
Valencia-Cadavid, Sara
Tomlinson, Simon R.
Kalathur, Ravi Kiran Reddy
Futschik, Matthias E.
De Sousa, Paul A.
dc.subject.por.fl_str_mv Dna Methylation
Transcription factor
Epigenetic signature
Gene-expression
Somatic-cells
Human Es
Culture
Differentiation
Lines
Pluripotency
topic Dna Methylation
Transcription factor
Epigenetic signature
Gene-expression
Somatic-cells
Human Es
Culture
Differentiation
Lines
Pluripotency
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
2015-07-01T00:00:00Z
2018-12-07T14:53:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/11442
url http://hdl.handle.net/10400.1/11442
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
10.1371/journal.pone.0131102
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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