Ontology highlight
ABSTRACT:
PROVIDER: PRJNA760795 | ENA |
REPOSITORIES: ENA
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Project 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.
2022-05-09 | PXD032792 | Pride
Project 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.
2022-05-06 | PXD028111 | Pride
Project 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.
2022-05-06 | PXD028162 | Pride
Project description:Induction of human trophoblast stem-like cells from primed pluripotent stem cells
| PRJNA737492 | ENA
Project description:Derivation of functional trophoblast stem cells from human primed pluripotent stem cells
| PRJNA757782 | ENA
Project description:Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3b signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters.Upon withdrawal of 2i/LIF, naM-CM-/ve mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalency acquisition on lineage regulatory genes. The feasibility for establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in rodent ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation of cross-species chimaeric embryos that underwent organogenesis following microinjection of human naive iPS cells into mouse morulas. Collectively, our findings establish new avenues for regenerative medicine, patient-specific iPS cell disease modelling and the study of early human development in vitro and in vivo. Four chromatin marks H3K4me1, H3K4me3, H3K27ac and H3K27me3 were measured from 3 cell lines: C1 and WIBR3 (naM-CM-/ve and conventional/primed stem cells), and BGO1 (only naM-CM-/ve stem cells).
2013-11-28 | E-GEOD-52617 | biostudies-arrayexpress
Project description:Here we show that by simple modulation of extrinsic signaling pathways, a new class of pluripotent stem cells, referred to as region selective epiblast stem cells (rsEpiSCs), could be efficiently derived from different stages of the early embryo. rsEpiSCs share features of primed pluripotency yet are distinct from EpiSCs in their molecular characteristics and ability to colonize post-implantation embryos. We performed ChIP-seqencing experiments using antibodies against H3K4me3 and H3K27me3, comparing conventional EpiSCs and rsEpiSCs, as well as comparing conventional human H1 ESCs and human H1 ESCs cultured in mouse rsEpiSCs based culture conditions (H1 rsESCs). Examination of 2 different histone modifications (H3K4me3, H3K27me3) in 2 pluripotent stem cell types in mouse and human.
2015-05-06 | E-GEOD-60604 | biostudies-arrayexpress
Project description:Placenta derived Okae et al. human trophoblast stem cells cultured in Okae et al. conditions (ttps://doi.org/10.1016/j.stem.2017.11.004). In addition, we sequenced SHEF6 primed human pluripotent stem cells as a control. Individual cells were manually isolated with a mouth pipette and subjected to single-cell full-lengths transcriptome profiling using a modified version of Smart-Seq2.
2022-06-03 | E-MTAB-10890 | biostudies-arrayexpress
Project description:Derivation of functional trophoblast stem cells from human primed pluripotent stem cells [scRNA-seq]
| PRJNA757786 | ENA
Project description:Derivation of functional trophoblast stem cells from human primed pluripotent stem cells [bulk RNA-seq]
| PRJNA757785 | ENA