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

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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.

Original language	English
Pages (from-to)	858-871
Number of pages	14
Journal	Nature Cell Biology
Volume	24
Issue number	6
DOIs	https://doi.org/10.1038/s41556-022-00932-w
State	Published - Jun 2022

Access to Document

10.1038/s41556-022-00932-w

Cite this

Zijlmans, D. W., Talon, I., Verhelst, S., Bendall, A., Van Nerum, K., Javali, A., Malcolm, A. A., van Knippenberg, S. S. F. A., 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, 24(6), 858-871. https://doi.org/10.1038/s41556-022-00932-w

@article{a8d2f6a354864630bbc2c24d5dfbd30b,

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 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.",

author = "Zijlmans, {Dick W.} and Irene Talon and Sigrid Verhelst and Adam Bendall and {Van Nerum}, Karlien and Alok Javali and Malcolm, {Andrew A.} and {van Knippenberg}, {Sam S.F.A.} 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",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jun,

doi = "10.1038/s41556-022-00932-w",

language = "English",

volume = "24",

pages = "858--871",

journal = "Nature Cell Biology",

issn = "1465-7392",

number = "6",

}

Zijlmans, DW, Talon, I, Verhelst, S, Bendall, A, Van Nerum, K, Javali, A, Malcolm, AA, van Knippenberg, SSFA, 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, vol. 24, no. 6, pp. 858-871. https://doi.org/10.1038/s41556-022-00932-w

TY - JOUR

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 - Van Nerum, Karlien

AU - Javali, Alok

AU - Malcolm, Andrew A.

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

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 - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85131042392&partnerID=8YFLogxK

U2 - 10.1038/s41556-022-00932-w

DO - 10.1038/s41556-022-00932-w

M3 - Article

C2 - 35697783

AN - SCOPUS:85131042392

SN - 1465-7392

VL - 24

SP - 858

EP - 871

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 6

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this