Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction

Autor: Dick W. Zijlmans, Irene Talon, Sigrid Verhelst, Adam Bendall, Karlien Van Nerum, Alok Javali, Andrew A. Malcolm, Sam S. F. A. van Knippenberg, Laura Biggins, San Kit To, Adrian Janiszewski, Danielle Admiraal, Ruth Knops, Nikky Corthout, Bradley P. Balaton, Grigorios Georgolopoulos, Amitesh Panda, Natarajan V. Bhanu, Amanda J. Collier, Charlene Fabian, Ryan N. Allsop, Joel Chappell, Thi Xuan Ai Pham, Michael Oberhuemer, Cankat Ertekin, Lotte Vanheer, Paraskevi Athanasouli, Frederic Lluis, Dieter Deforce, Joop H. Jansen, Benjamin A. Garcia, Michiel Vermeulen, Nicolas Rivron, Maarten Dhaenens, Hendrik Marks, Peter J. Rugg-Gunn, Vincent Pasque
Přispěvatelé: Talon, Irene [0000-0002-5800-5555], Verhelst, Sigrid [0000-0002-6791-3782], Bendall, Adam [0000-0002-6865-2625], Van Nerum, Karlien [0000-0002-8952-5473], Malcolm, Andrew A [0000-0001-6240-7701], van Knippenberg, Sam SFA [0000-0001-5656-3046], To, San Kit [0000-0002-3057-2902], Balaton, Bradley P [0000-0002-5130-7868], Panda, Amitesh [0000-0002-2702-3494], Pham, Thi Xuan Ai [0000-0003-3866-2002], Oberhuemer, Michael [0000-0003-2273-2782], Deforce, Dieter [0000-0002-0635-661X], Vermeulen, Michiel [0000-0003-0836-6894], Rivron, Nicolas [0000-0003-1590-5964], Dhaenens, Maarten [0000-0002-9801-3509], Marks, Hendrik [0000-0002-4198-3731], Rugg-Gunn, Peter J [0000-0002-9601-5949], Pasque, Vincent [0000-0002-5129-0146], Apollo - University of Cambridge Repository, Malcolm, Andrew [0000-0001-6240-7701]
Rok vydání: 2022
Předmět:
Zdroj: Nature Cell Biology, 24, pp. 858-871
Nature Cell Biology, 24, 858-871
Nature Cell Biology
NATURE CELL BIOLOGY
ISSN: 1476-4679
1465-7392
DOI: 10.1038/s41556-022-00932-w
Popis: Funder: The Marks lab is supported by an NWO-XS grant
Funder: M.V. is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society
Funder: D.W.Z. is part of the Oncode Institute, which is partly funded by the Dutch Cancer Society
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.
Databáze: OpenAIRE