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 |
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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: |
CHROMATIN
EXPRESSION DYNAMICS Pluripotent Stem Cells 631/136/2444 101 Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] PROTEIN 13/106 BLASTOCYST macromolecular substances R/BIOCONDUCTOR PACKAGE 13 PLURIPOTENCY 14 38/91 Histones 13/1 All institutes and research themes of the Radboud University Medical Center 631/337/176 Humans TRANSCRIPTION 96/1 14/19 Molecular Biology 42 Science & Technology 45 82/58 Proteomics and Chromatin Biology 631/136/532/2062 article Polycomb Repressive Complex 2 Biology and Life Sciences Cell Differentiation Cell Biology NAIVE 45/15 Chromatin Trophoblasts 13/31 13/51 14/63 631/337/100 38/39 45/100 EMBRYONIC STEM-CELLS Life Sciences & Biomedicine |
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 |
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