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dc.contributor.authorZijlmans, Dick W
dc.contributor.authorTalon, Irene
dc.contributor.authorVerhelst, Sigrid
dc.contributor.authorBendall, Adam
dc.contributor.authorVan Nerum, Karlien
dc.contributor.authorJavali, Alok
dc.contributor.authorMalcolm, Andrew
dc.contributor.authorvan Knippenberg, Sam SFA
dc.contributor.authorBiggins, Laura
dc.contributor.authorTo, San Kit
dc.contributor.authorJaniszewski, Adrian
dc.contributor.authorAdmiraal, Danielle
dc.contributor.authorKnops, Ruth
dc.contributor.authorCorthout, Nikky
dc.contributor.authorBalaton, Bradley P
dc.contributor.authorGeorgolopoulos, Grigorios
dc.contributor.authorPanda, Amitesh
dc.contributor.authorBhanu, Natarajan V
dc.contributor.authorCollier, Amanda J
dc.contributor.authorFabian, Charlene
dc.contributor.authorAllsop, Ryan N
dc.contributor.authorChappell, Joel
dc.contributor.authorPham, Thi Xuan Ai
dc.contributor.authorOberhuemer, Michael
dc.contributor.authorErtekin, Cankat
dc.contributor.authorVanheer, Lotte
dc.contributor.authorAthanasouli, Paraskevi
dc.contributor.authorLluis, Frederic
dc.contributor.authorDeforce, Dieter
dc.contributor.authorJansen, Joop H
dc.contributor.authorGarcia, Benjamin A
dc.contributor.authorVermeulen, Michiel
dc.contributor.authorRivron, Nicolas
dc.contributor.authorDhaenens, Maarten
dc.contributor.authorMarks, Hendrik
dc.contributor.authorRugg-Gunn, Peter J
dc.contributor.authorPasque, Vincent
dc.date.accessioned2022-06-16T16:00:25Z
dc.date.available2022-06-16T16:00:25Z
dc.date.issued2022-06
dc.date.submitted2021-09-02
dc.identifier.issn1465-7392
dc.identifier.others41556-022-00932-w
dc.identifier.other932
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338161
dc.descriptionFunder: D.W.Z. is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society
dc.descriptionFunder: M.V. is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society
dc.descriptionFunder: The Marks lab is supported by an NWO-XS grant (OCENW.XS5.052)
dc.description.abstractHuman naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stem cells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition of PRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/136/532/2062
dc.subject/631/136/2444
dc.subject/631/337/176
dc.subject/631/337/100
dc.subject/13
dc.subject/13/1
dc.subject/14
dc.subject/13/51
dc.subject/13/31
dc.subject/13/106
dc.subject/38/39
dc.subject/38/91
dc.subject/45/15
dc.subject/45/100
dc.subject/82/58
dc.subject/14/19
dc.subject/101
dc.subject/96/1
dc.subject/14/63
dc.subject/42
dc.subject/45
dc.subjectarticle
dc.titleIntegrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction.
dc.typeArticle
dc.date.updated2022-06-16T16:00:24Z
prism.endingPage871
prism.issueIdentifier6
prism.publicationNameNat Cell Biol
prism.startingPage858
prism.volume24
dc.identifier.doi10.17863/CAM.85572
dcterms.dateAccepted2022-05-05
rioxxterms.versionofrecord10.1038/s41556-022-00932-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidTalon, Irene [0000-0002-5800-5555]
dc.contributor.orcidVerhelst, Sigrid [0000-0002-6791-3782]
dc.contributor.orcidBendall, Adam [0000-0002-6865-2625]
dc.contributor.orcidVan Nerum, Karlien [0000-0002-8952-5473]
dc.contributor.orcidMalcolm, Andrew [0000-0001-6240-7701]
dc.contributor.orcidvan Knippenberg, Sam SFA [0000-0001-5656-3046]
dc.contributor.orcidTo, San Kit [0000-0002-3057-2902]
dc.contributor.orcidBalaton, Bradley P [0000-0002-5130-7868]
dc.contributor.orcidPanda, Amitesh [0000-0002-2702-3494]
dc.contributor.orcidPham, Thi Xuan Ai [0000-0003-3866-2002]
dc.contributor.orcidOberhuemer, Michael [0000-0003-2273-2782]
dc.contributor.orcidDeforce, Dieter [0000-0002-0635-661X]
dc.contributor.orcidVermeulen, Michiel [0000-0003-0836-6894]
dc.contributor.orcidRivron, Nicolas [0000-0003-1590-5964]
dc.contributor.orcidDhaenens, Maarten [0000-0002-9801-3509]
dc.contributor.orcidMarks, Hendrik [0000-0002-4198-3731]
dc.contributor.orcidRugg-Gunn, Peter J [0000-0002-9601-5949]
dc.contributor.orcidPasque, Vincent [0000-0002-5129-0146]
dc.identifier.eissn1476-4679
pubs.funder-project-idFonds Wetenschappelijk Onderzoek (Research Foundation Flanders) (1S72719N, 3S031319, 1S75720N, 1158318N, 11L0722N, 11N3122N, 1S29419N, 12E9716N, G0C9320N, G0B4420N)
pubs.funder-project-idU.S. Department of Health & Human Services | National Institutes of Health (NIH) (P01CA196539, AG031862)
pubs.funder-project-idRCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/B/000C0421, BBS/E/B/000C0422)
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/T011769/1, MR/N018419/1)
cam.issuedOnline2022-06-13


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