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

被引：40

作者：

Zijlmans, Dick W. ^{[1
]}

Talon, Irene ^{[2
]}

Verhelst, Sigrid ^{[3
]}

Bendall, Adam ^{[4
]}

Van Nerum, Karlien ^{[2
]}

Javali, Alok ^{[5
]}

Malcolm, Andrew A. ^{[4
,6
]}

van Knippenberg, Sam S. F. A. ^{[2
]}

Biggins, Laura ^{[7
]}

To, San Kit ^{[2
]}

Janiszewski, Adrian ^{[2
]}

Admiraal, Danielle ^{[8
]}

Knops, Ruth ^{[9
]}

Corthout, Nikky ^{[10
]}

Balaton, Bradley P. ^{[2
]}

Georgolopoulos, Grigorios ^{[2
]}

Panda, Amitesh ^{[2
]}

Bhanu, Natarajan, V ^{[11
]}

Collier, Amanda J. ^{[4
]}

Fabian, Charlene ^{[4
]}

Allsop, Ryan N. ^{[2
]}

Chappell, Joel ^{[2
]}

Thi Xuan Ai Pham ^{[2
]}

Oberhuemer, Michael ^{[2
]}

Ertekin, Cankat ^{[2
]}

Vanheer, Lotte ^{[2
]}

Athanasouli, Paraskevi ^{[2
]}

Lluis, Frederic ^{[2
]}

Deforce, Dieter ^{[3
]}

Jansen, Joop H. ^{[9
]}

Garcia, Benjamin A. ^{[11
]}

Vermeulen, Michiel ^{[1
,8
]}

Rivron, Nicolas ^{[5
]}

Dhaenens, Maarten ^{[3
]}

Marks, Hendrik ^{[8
]}

Rugg-Gunn, Peter J. ^{[4
,6
,12
]}

Pasque, Vincent ^{[2
]}

机构：

[1] Radboud Univ Nijmegen, Dept Mol Biol, Fac Sci, Radboud Inst Mol Life Sci RIMLS,Oncode Inst, Nijmegen, Netherlands

[2] Katholieke Univ Leuven, Leuven Inst Single Cell Omics LISCO, Dept Dev & Regenerat, Leuven Stem Cell Inst, Leuven, Belgium

[3] Univ Ghent, Lab Pharmaceut Biotechnol, ProGenT, Ghent, Belgium

[4] Babraham Inst, Epigenet Programme, Cambridge, England

[5] Austrian Acad Sci, Inst Mol Biotechnol, Vienna, Austria

[6] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England

[7] Babraham Inst, Bioinformat Grp, Cambridge, England

[8] Radboud Univ Nijmegen, Fac Sci, Radboud Inst Mol Life Sci RIMLS, Dept Mol Biol, Nijmegen, Netherlands

[9] Radboud Univ Nijmegen Med Ctr RadboudUMC, Dept Lab Med, Lab Hematol, Nijmegen, Netherlands

[10] Katholieke Univ Leuven, VIB Bioimaging Core, NIB Ctr Brain & Dis Res, Leuven, Belgium

[11] Univ Penn, Epigenet Inst, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA

[12] Univ Cambridge, Ctr Trophoblast Res, Cambridge, England

来源：

NATURE CELL BIOLOGY | 2022年 / 24卷 / 06期

基金：

欧洲研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

EMBRYONIC STEM-CELLS; R/BIOCONDUCTOR PACKAGE; NAIVE; PLURIPOTENCY; CHROMATIN; EXPRESSION; PROTEIN; TRANSCRIPTION; BLASTOCYST; DYNAMICS;

D O I：

10.1038/s41556-022-00932-w

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Two side-by-side papers report that H3K27me3 deposited by polycomb repressive complex 2 represents an epigenetic barrier that restricts naive human pluripotent cell differentiation into alternative lineages including trophoblasts. 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.

引用

页码：858 / +

页数：41

共 110 条

[41] HIstome-a relational knowledgebase of human histone proteins and histone modifying enzymes
Khare, Satyajeet P.
Habib, Farhat
Sharma, Rahul
Gadewal, Nikhil
Gupta, Sanjay
Galande, Sanjeev
[J]. NUCLEIC ACIDS RESEARCH, 2012, 40 (D1) : D337 - D342
[42] Parallel derivation of isogenic human primed and naive induced pluripotent stem cells
Kilens, Stephanie
Meistermann, Dimitri
Moreno, Diego
Chariau, Caroline
Gaignerie, Anne
Reignier, Arnaud
Lelievre, Yohann
Casanova, Miguel
Vallot, Celine
Nedellec, Steven
Flippe, Lea
Firmin, Julie
Song, Juan
Charpentier, Eric
Lammers, Jenna
Donnart, Audrey
Marec, Nadege
Deb, Wallid
Bihouee, Audrey
Le Caignec, Cedric
Pecqueur, Claire
Redon, Richard
Barriere, Paul
Bourdon, Jeremie
Pasque, Vincent
Soumillon, Magali
Mikkelsen, Tarjei S.
Rougeulle, Claire
Freour, Thomas
David, Laurent
[J]. NATURE COMMUNICATIONS, 2018, 9
[43] Konze KD, 2013, ACS CHEM BIOL, V8, P1324, DOI [10.1021/cb400133J, 10.1021/cb400133j]
[44] The UCSC genome browser and associated tools
Kuhn, Robert M.
Haussler, David
Kent, W. James
[J]. BRIEFINGS IN BIOINFORMATICS, 2013, 14 (02) : 144 - 161
[45] Polycomb repressive complex 2 shields naive human pluripotent cells from trophectoderm differentiation
Kumar, Banushree
Navarro, Carmen
Winblad, Nerges
Schell, John P.
Zhao, Cheng
Weltner, Jere
Baque-Vidal, Laura
Salazar Mantero, Angelo
Petropoulos, Sophie
Lanner, Fredrik
Elsasser, Simon J.
[J]. NATURE CELL BIOLOGY, 2022, 24 (06) : 845 - +
[46] Chromatin enrichment for proteomics
Kustatscher, Georg
Wills, Karen L. H.
Furlan, Cristina
Rappsilber, Juri
[J]. NATURE PROTOCOLS, 2014, 9 (09) : 2090 - 2099
[47] Langmead B, 2012, NAT METHODS, V9, P357, DOI [10.1038/NMETH.1923, 10.1038/nmeth.1923]
[48] WashU Epigenome Browser update 2019
Li, Daofeng
Hsu, Silas
Purushotham, Deepak
Sears, Renee L.
Wang, Ting
[J]. NUCLEIC ACIDS RESEARCH, 2019, 47 (W1) : W158 - W165
[49] Li H, 2009, BIOINFORMATICS, V25, P1094, DOI [10.1093/bioinformatics/btp100, 10.1093/bioinformatics/btp324]
[50] CTCF regulates allelic expression of Igf2 by orchestrating a promoter-polycomb repressive complex 2 intrachromosomal loop
Li, Tao
Hu, Ji-Fan
Qiu, Xinwen
Ling, Jianqun
Chen, Huiling
Wang, Shukui
Hou, Aiju
Vu, Thanh H.
Hoffman, Andrew R.
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (20) : 6473 - 6482

← 1 2 3 4 5 6 7 8 9 10 →