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
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

858-871

Subventions

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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Auteurs

Dick W Zijlmans (DW)

Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands.

Irene Talon (I)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Sigrid Verhelst (S)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Adam Bendall (A)

Epigenetics Programme, Babraham Institute, Cambridge, UK.

Karlien Van Nerum (K)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Alok Javali (A)

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

Andrew A Malcolm (AA)

Epigenetics Programme, Babraham Institute, Cambridge, UK.
The Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Sam S F A van Knippenberg (SSFA)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Laura Biggins (L)

Bioinformatics Group, Babraham Institute, Cambridge, UK.

San Kit To (SK)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Adrian Janiszewski (A)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Danielle Admiraal (D)

Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Nijmegen, Nijmegen, The Netherlands.

Ruth Knops (R)

Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre (RadboudUMC), Nijmegen, the Netherlands.

Nikky Corthout (N)

VIB Center for Brain and Disease Research, KU Leuven, VIB Bioimaging Core, Leuven, Belgium.

Bradley P Balaton (BP)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Grigorios Georgolopoulos (G)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Amitesh Panda (A)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Natarajan V Bhanu (NV)

Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Amanda J Collier (AJ)

Epigenetics Programme, Babraham Institute, Cambridge, UK.

Charlene Fabian (C)

Epigenetics Programme, Babraham Institute, Cambridge, UK.

Ryan N Allsop (RN)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Joel Chappell (J)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Thi Xuan Ai Pham (TXA)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Michael Oberhuemer (M)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Cankat Ertekin (C)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Lotte Vanheer (L)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Paraskevi Athanasouli (P)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Frederic Lluis (F)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium.

Dieter Deforce (D)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.

Joop H Jansen (JH)

Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre (RadboudUMC), Nijmegen, the Netherlands.

Benjamin A Garcia (BA)

Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Michiel Vermeulen (M)

Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands.
Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Nijmegen, Nijmegen, The Netherlands.

Nicolas Rivron (N)

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

Maarten Dhaenens (M)

ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium. Maarten.Dhaenens@UGent.be.

Hendrik Marks (H)

Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Nijmegen, Nijmegen, The Netherlands. Hendrik.Marks@ru.nl.

Peter J Rugg-Gunn (PJ)

Epigenetics Programme, Babraham Institute, Cambridge, UK. peter.rugg-gunn@babraham.ac.uk.
The Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. peter.rugg-gunn@babraham.ac.uk.
The Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. peter.rugg-gunn@babraham.ac.uk.

Vincent Pasque (V)

Department of Development and Regeneration, Leuven Stem Cell Institute, Leuven Institute for Single Cell Omics (LISCO), KU Leuven, Leuven, Belgium. vincent.pasque@kuleuven.be.

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