Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
02
09
2021
accepted:
05
05
2022
pubmed:
14
6
2022
medline:
22
6
2022
entrez:
13
6
2022
Statut:
ppublish
Résumé
Human 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.
Identifiants
pubmed: 35697783
doi: 10.1038/s41556-022-00932-w
pii: 10.1038/s41556-022-00932-w
pmc: PMC9203278
doi:
Substances chimiques
Chromatin
0
Histones
0
Polycomb Repressive Complex 2
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
858-871Subventions
Organisme : Wellcome Trust
ID : 102160/Z/13/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P01 CA196539
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0421
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P01 AG031862
Pays : United States
Organisme : Wellcome Trust
ID : 215116/Z/18/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0422
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI118891
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N018419/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V02969X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J003808/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T011769/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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