{"id":["DOI:10.1038/s41556-022-00932-w"],"title":["Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction"],"publication_date":["2024-11-20"],"authors":{"ORCID:0000-0003-1527-1834":{"id":["ORCID:0000-0003-1527-1834"],"family_name":["Zijlmans"],"personal_name":["Dick W."],"affiliations":{"ROR:01yb10j39":{"organization_name":["Radboud Institute for Molecular Life Sciences"]}}},"ORCID:0000-0002-5800-5555":{"id":["ORCID:0000-0002-5800-5555"],"family_name":["Talon"],"personal_name":["Irene"],"affiliations":{"ROR:05f950310":{"organization_name":["KU Leuven"]}}},"ORCID:0000-0002-6791-3782":{"id":["ORCID:0000-0002-6791-3782"],"family_name":["Verhelst"],"personal_name":["Sigrid"],"affiliations":{"ROR:00cv9y106":{"organization_name":["Ghent University"]}}},"ORCID:0000-0002-8952-5473":{"id":["ORCID:0000-0002-8952-5473"],"family_name":["Van Nerum"],"personal_name":["Karlien"],"affiliations":{"ROR:05f950310":{"organization_name":["KU Leuven"]}}},"ORCID:0000-0002-8769-0272":{"id":["ORCID:0000-0002-8769-0272"],"family_name":["Javali"],"personal_name":["Alok"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0001-6240-7701":{"id":["ORCID:0000-0001-6240-7701"],"family_name":["Malcolm"],"personal_name":["Andrew A."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]}}},"ORCID:0000-0001-5656-3046":{"id":["ORCID:0000-0001-5656-3046"],"family_name":["van Knippenberg"],"personal_name":["Sam S. 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Leuven"]}}},"ORCID:0000-0002-7296-7611":{"id":["ORCID:0000-0002-7296-7611"],"family_name":["Lluis"],"personal_name":["Frederic"],"affiliations":{"ROR:05f950310":{"organization_name":["KU Leuven"]}}},"ORCID:0000-0002-0635-661X":{"id":["ORCID:0000-0002-0635-661X"],"family_name":["Deforce"],"personal_name":["Dieter"],"affiliations":{"ROR:00cv9y106":{"organization_name":["Ghent University"]}}},"ORCID:0000-0001-9459-568X":{"id":["ORCID:0000-0001-9459-568X"],"family_name":["Jansen"],"personal_name":["Joop H."],"affiliations":{"ROR:01yb10j39":{"organization_name":["Radboud Institute for Molecular Life Sciences"]}}},"ORCID:0000-0002-2306-1207":{"id":["ORCID:0000-0002-2306-1207"],"family_name":["Garcia"],"personal_name":["Benjamin A."],"affiliations":{"ROR:00b30xv10":{"organization_name":["University of Pennsylvania"]}}},"ORCID:0000-0003-0836-6894":{"id":["ORCID:0000-0003-0836-6894"],"family_name":["Vermeulen"],"personal_name":["Michiel"],"affiliations":{"ROR:01yb10j39":{"organization_name":["Radboud Institute for Molecular Life Sciences"]}}},"ORCID:0000-0003-1590-5964":{"id":["ORCID:0000-0003-1590-5964"],"family_name":["Rivron"],"personal_name":["Nicolas"],"affiliations":{"ROR:01zqrxf85":{"organization_name":["Institute of Molecular Biotechnology"]}}},"ORCID:0000-0002-9801-3509":{"id":["ORCID:0000-0002-9801-3509"],"family_name":["Dhaenens"],"personal_name":["Maarten"],"affiliations":{"ROR:00cv9y106":{"organization_name":["Ghent University"]}}},"ORCID:0000-0002-4198-3731":{"id":["ORCID:0000-0002-4198-3731"],"family_name":["Marks"],"personal_name":["Hendrik"],"affiliations":{"ROR:01yb10j39":{"organization_name":["Radboud Institute for Molecular Life Sciences"]}}},"ORCID:0000-0002-9601-5949":{"id":["ORCID:0000-0002-9601-5949"],"family_name":["Rugg-Gunn"],"personal_name":["Peter J."],"affiliations":{"1":{}},"HDBItheme":["Early"]},"ORCID:0000-0002-5129-0146":{"id":["ORCID:0000-0002-5129-0146"],"family_name":["Pasque"],"personal_name":["Vincent"],"affiliations":{"ROR:05f950310":{"organization_name":["KU Leuven"]}}}},"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."],"HDBItheme":["Early"],"datasets":{"GEO:GSE176175":{"id":["GEO:GSE176175"],"title":["Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction."],"description":["This SuperSeries is composed of the following SubSeries:\n\n- GSE176172\tBulk RNAsequencing of H9 Primed and Naïve Pluripotent Stem Cells with and without EZH2 inhibition.\n- GSE176173\tSingle-Cell RNAsequencing of Human Naïve Pluripotent Stem Cells to Trophoblast Stem Cells with and without EZH2 inhibition.\n- GSE183735\tCUT & RUN H3K27me3 of Human Naïve and Primed Pluripotent Stem Cells with and without EZH2 inhibition."],"authors":{"ORCID:0000-0002-5129-0146":{"id":["ORCID:0000-0002-5129-0146"],"family_name":["Pasque"],"personal_name":["Vincent"],"affiliations":{"ROR:05f950310":{"organization_name":["KU Leuven"]}}}},"tags":["sequencing"]},"PRIDE:PXD028162":{"id":["PRIDE:PXD028162"],"title":["Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction"],"description":["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 apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. 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. Data originating from the LC-MS/MS analysis of the histone PTMs can be consulted via this project."],"authors":{"ORCID:0000-0002-9801-3509":{"id":["ORCID:0000-0002-9801-3509"],"family_name":["Dhaenens"],"personal_name":["Maarten"],"affiliations":{"ROR:00cv9y106":{"organization_name":["Ghent University"]}}}},"tags":["proteomics"]},"PRIDE:PXD032792":{"id":["PRIDE:PXD032792"],"title":["Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction"],"description":["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 naive pluripotent stem cell chromatin, 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, while 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."],"authors":{"AUTHTEMP:00071":{"id":["AUTHTEMP:00071"],"family_name":["Bhanu"],"personal_name":["Natarajan V."],"affiliations":{"ROR:00b30xv10":{"organization_name":["University of Pennsylvania"]}}},"ORCID:0000-0002-2306-1207":{"id":["ORCID:0000-0002-2306-1207"],"family_name":["Garcia"],"personal_name":["Benjamin A."],"affiliations":{"ROR:00b30xv10":{"organization_name":["University of Pennsylvania"]}}}},"tags":["proteomics"]},"PRIDE:PXD028111":{"id":["PRIDE:PXD028111"],"title":["Polycomb Repressive Complex 2 Restricts Human Naive Pluripotent Stem Cell to Trophoblast Fate Induction"],"description":["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 apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. 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."],"authors":{"ORCID:0000-0003-1527-1834":{"id":["ORCID:0000-0003-1527-1834"],"family_name":["Zijlmans"],"personal_name":["Dick W."],"affiliations":{"ROR:01yb10j39":{"organization_name":["Radboud Institute for Molecular Life Sciences"]}}},"ORCID:0000-0002-4198-3731":{"id":["ORCID:0000-0002-4198-3731"],"family_name":["Marks"],"personal_name":["Hendrik"],"affiliations":{"ROR:01yb10j39":{"organization_name":["Radboud Institute for Molecular Life Sciences"]}}}},"tags":["proteomics"]}},"code":{"DOI:10.5281/ZENODO.6398543":{"id":["DOI:10.5281/ZENODO.6398543"],"title":["pasquelab/PRC2: Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction"],"description":["Scripts related to the manuscript \"Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction\" from The Pasque Lab."],"authors":{}},"DOI:10.5281/ZENODO.6400749":{"id":["DOI:10.5281/ZENODO.6400749"],"title":["Chromatin and histone proteomics of human pluripotent states"],"description":["Shiny application that allows the exploration of datasets associated with the paper Integrated Multi-Omics Reveal Polycomb Repressive Complex 2 Restricts Human Trophoblast Induction. \nThe app is hosted here: https://www.bioinformatics.babraham.ac.uk/shiny/shiny_omics/Shiny_omics/"],"authors":{"ORCID:0000-0002-0975-1121":{"id":["ORCID:0000-0002-0975-1121"],"family_name":["Biggins"],"personal_name":["Laura"],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]}}}}},"DOI:10.5281/ZENODO.6399297":{"id":["DOI:10.5281/ZENODO.6399297"],"title":["Scripts required for processing and visualisation of calibrated Cut&Run data as published in Zijlmans et al., 2022."],"description":["Scripts detailing calibrated Cut&Run analysis for Zijlmans et al., 2022. Scripts allow for processing of bam files to bigwig files. Scripts used for analysis and visualisation are provided."],"authors":{"ORCID:0000-0001-6240-7701":{"id":["ORCID:0000-0001-6240-7701"],"family_name":["Malcolm"],"personal_name":["Andrew A."],"affiliations":{"ROR:01d5qpn59":{"organization_name":["Babraham Institute"]},"ROR:05nz0zp31":{"organization_name":["Wellcome/MRC Cambridge Stem Cell Institute"]}}}}}}}