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

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

doi:10.1038/s41556-022-00932-w

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

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 FabianRyan 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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

47 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Cell Biology
Antal sider	41
ISSN	1465-7392
DOI	https://doi.org/10.1038/s41556-022-00932-w
Status	Udgivet - 2022
Udgivet eksternt	Ja

Adgang til dokumentet

10.1038/s41556-022-00932-w

Citationsformater

Zijlmans, D. W., Talon, I., Verhelst, S., Bendall, A., Nerum, K. V., Javali, A., Malcolm, A. A., Knippenberg, S. S. F. A. V., Biggins, L., To, S. K., Janiszewski, A., Admiraal, D., Knops, R., Corthout, N., Balaton, B. P., Georgolopoulos, G., Panda, A., Bhanu, N. V., Collier, A. J., ... Pasque, V. (2022). Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction. Nature Cell Biology. https://doi.org/10.1038/s41556-022-00932-w

Zijlmans, DW, Talon, I, Verhelst, S, Bendall, A, Nerum, KV, Javali, A, Malcolm, AA, Knippenberg, SSFAV, Biggins, L, To, SK, Janiszewski, A, Admiraal, D, Knops, R, Corthout, N, Balaton, BP, Georgolopoulos, G, Panda, A, Bhanu, NV, Collier, AJ, Fabian, C, Allsop, RN, Chappell, J, Pham, TXA, Oberhuemer, M, Ertekin, C, Vanheer, L, Athanasouli, P, Lluis, F, Deforce, D, Jansen, JH, Garcia, BA, Vermeulen, M, Rivron, N, Dhaenens, M, Marks, H, Rugg-Gunn, PJ & Pasque, V 2022, 'Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction', Nature Cell Biology. https://doi.org/10.1038/s41556-022-00932-w

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title = "Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction",

abstract = "Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought tolack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associatedproteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Ourintegrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify astrong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stemcells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activityacts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition ofPRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that humannaive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose theinduction of alternative cell fates.",

author = "Zijlmans, {Dick W.} and Irene Talon and Sigrid Verhelst and Adam Bendall and Nerum, {Karlien Van} and Alok Javali and Malcolm, {Andrew A.} and Knippenberg, {Sam S. F. A. van} and Laura Biggins and To, {San Kit} and Adrian Janiszewski and Danielle Admiraal and Ruth Knops and Nikky Corthout and Balaton, {Bradley P.} and Grigorios Georgolopoulos and Amitesh Panda and Bhanu, {Natarajan V.} and Collier, {Amanda J.} and Charlene Fabian and Allsop, {Ryan N.} and Joel Chappell and Pham, {Thi Xuan Ai} and Michael Oberhuemer and Cankat Ertekin and Lotte Vanheer and Paraskevi Athanasouli and Frederic Lluis and Dieter Deforce and Jansen, {Joop H.} and Garcia, {Benjamin A.} and Michiel Vermeulen and Nicolas Rivron and Maarten Dhaenens and Hendrik Marks and Rugg-Gunn, {Peter J.} and Vincent Pasque",

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T1 - Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction

AU - Zijlmans, Dick W.

AU - Talon, Irene

AU - Verhelst, Sigrid

AU - Bendall, Adam

AU - Nerum, Karlien Van

AU - Javali, Alok

AU - Malcolm, Andrew A.

AU - Knippenberg, Sam S. F. A. van

AU - Biggins, Laura

AU - To, San Kit

AU - Janiszewski, Adrian

AU - Admiraal, Danielle

AU - Knops, Ruth

AU - Corthout, Nikky

AU - Balaton, Bradley P.

AU - Georgolopoulos, Grigorios

AU - Panda, Amitesh

AU - Bhanu, Natarajan V.

AU - Collier, Amanda J.

AU - Fabian, Charlene

AU - Allsop, Ryan N.

AU - Chappell, Joel

AU - Pham, Thi Xuan Ai

AU - Oberhuemer, Michael

AU - Ertekin, Cankat

AU - Vanheer, Lotte

AU - Athanasouli, Paraskevi

AU - Lluis, Frederic

AU - Deforce, Dieter

AU - Jansen, Joop H.

AU - Garcia, Benjamin A.

AU - Vermeulen, Michiel

AU - Rivron, Nicolas

AU - Dhaenens, Maarten

AU - Marks, Hendrik

AU - Rugg-Gunn, Peter J.

AU - Pasque, Vincent

PY - 2022

Y1 - 2022

N2 - Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought tolack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associatedproteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Ourintegrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify astrong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stemcells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activityacts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition ofPRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that humannaive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose theinduction of alternative cell fates.

AB - Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought tolack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associatedproteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Ourintegrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify astrong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stemcells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activityacts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition ofPRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that humannaive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose theinduction of alternative cell fates.

U2 - 10.1038/s41556-022-00932-w

DO - 10.1038/s41556-022-00932-w

M3 - Journal article

C2 - 35697783

SN - 1465-7392

JO - Nature Cell Biology

JF - Nature Cell Biology

ER -