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

Dick W. Zijlmans, Irene Talon, Sigrid Verhelst (UGent) , Adam Bendall, Karlien Van Nerum, Alok Javali, Andrew A. Malcolm, Sam S. F. A. van Knippenberg, Laura Biggins, San Kit To, et al.
(2022) NATURE CELL BIOLOGY. 24(6). p.858-871
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Abstract
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.</jats:p>
Keywords
Cell Biology, EMBRYONIC STEM-CELLS, R/BIOCONDUCTOR PACKAGE, NAIVE, PLURIPOTENCY, CHROMATIN, EXPRESSION, PROTEIN, TRANSCRIPTION, BLASTOCYST, DYNAMICS

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MLA
Zijlmans, Dick W., et al. “Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction.” NATURE CELL BIOLOGY, vol. 24, no. 6, 2022, pp. 858–71, doi:10.1038/s41556-022-00932-w.
APA
Zijlmans, D. W., Talon, I., Verhelst, S., Bendall, A., Van Nerum, K., Javali, A., … Pasque, V. (2022). Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction. NATURE CELL BIOLOGY, 24(6), 858–871. https://doi.org/10.1038/s41556-022-00932-w
Chicago author-date
Zijlmans, Dick W., Irene Talon, Sigrid Verhelst, Adam Bendall, Karlien Van Nerum, Alok Javali, Andrew A. Malcolm, et al. 2022. “Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction.” NATURE CELL BIOLOGY 24 (6): 858–71. https://doi.org/10.1038/s41556-022-00932-w.
Chicago author-date (all authors)
Zijlmans, Dick W., 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, and Vincent Pasque. 2022. “Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction.” NATURE CELL BIOLOGY 24 (6): 858–871. doi:10.1038/s41556-022-00932-w.
Vancouver
1.
Zijlmans DW, Talon I, Verhelst S, Bendall A, Van Nerum K, Javali A, et al. Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction. NATURE CELL BIOLOGY. 2022;24(6):858–71.
IEEE
[1]
D. W. Zijlmans et al., “Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction,” NATURE CELL BIOLOGY, vol. 24, no. 6, pp. 858–871, 2022.
@article{8756363,
  abstract     = {{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.</jats:p>}},
  author       = {{Zijlmans, Dick W. and Talon, Irene and Verhelst, Sigrid and Bendall, Adam and Van Nerum, Karlien and Javali, Alok and Malcolm, Andrew A. and van Knippenberg, Sam S. F. A. and Biggins, Laura and To, San Kit and Janiszewski, Adrian and Admiraal, Danielle and Knops, Ruth and Corthout, Nikky and Balaton, Bradley P. and Georgolopoulos, Grigorios and Panda, Amitesh and Bhanu, Natarajan V. and Collier, Amanda J. and Fabian, Charlene and Allsop, Ryan N. and Chappell, Joel and Pham, Thi Xuan Ai and Oberhuemer, Michael and Ertekin, Cankat and Vanheer, Lotte and Athanasouli, Paraskevi and Lluis, Frederic and Deforce, Dieter and Jansen, Joop H. and Garcia, Benjamin A. and Vermeulen, Michiel and Rivron, Nicolas and Dhaenens, Maarten and Marks, Hendrik and Rugg-Gunn, Peter J. and Pasque, Vincent}},
  issn         = {{1465-7392}},
  journal      = {{NATURE CELL BIOLOGY}},
  keywords     = {{Cell Biology,EMBRYONIC STEM-CELLS,R/BIOCONDUCTOR PACKAGE,NAIVE,PLURIPOTENCY,CHROMATIN,EXPRESSION,PROTEIN,TRANSCRIPTION,BLASTOCYST,DYNAMICS}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{858--871}},
  title        = {{Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction}},
  url          = {{http://doi.org/10.1038/s41556-022-00932-w}},
  volume       = {{24}},
  year         = {{2022}},
}
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