Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1086168 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Naïve pluripotent stem cells (nPSCs) correspond to nascent epiblast in the pre-implantation embryo. nPSCs from mouse and human differ in self-renewal requirements and potency for trophectoderm generation. Here we investigated chimpanzee (Pan troglodytes) nPSCs. Naïve type colonies emerged after resetting or reprogramming but failed to expand. We found that the block to self-renewal is overcome by inhibition of EZH2, the enzymatic component of Polycomb repressor group 2 (PRC2). Chimpanzee nPSCs are euploid, produce teratomas, and can be capacitated for somatic lineage differentiation in vitro. They show transcriptome relatedness to human nPSCs and early epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee nPSCs differentiate to trophectoderm and form tri-lineage blastoids. We confirmed that PRC2 suppresses self-renewal by genetic deletions. Furthermore, we demonstrate that EZH2 inhibition facilitates feeder-free propagation of human nPSCs. In summary, chimpanzee nPSCs expand the repertoire of systems for studying primate pluripotency and early embryogenesis.
2025-02-26 | GSE282157 | GEO
Project description:Naïve pluripotent stem cells (nPSCs) correspond to nascent epiblast in the pre-implantation embryo. nPSCs from mouse and human differ in self-renewal requirements and potency for trophectoderm generation. Here we investigated chimpanzee (Pan troglodytes) nPSCs. Naïve type colonies emerged after resetting or reprogramming but failed to expand. We found that the block to self-renewal is overcome by inhibition of EZH2, the enzymatic component of Polycomb repressor group 2 (PRC2). Chimpanzee nPSCs are euploid, produce teratomas, and can be capacitated for somatic lineage differentiation in vitro. They show transcriptome relatedness to human nPSCs and early epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee nPSCs differentiate to trophectoderm and form tri-lineage blastoids. We confirmed that PRC2 suppresses self-renewal by genetic deletions. Furthermore, we demonstrate that EZH2 inhibition facilitates feeder-free propagation of human nPSCs. In summary, chimpanzee nPSCs expand the repertoire of systems for studying primate pluripotency and early embryogenesis.
2025-02-26 | GSE264735 | GEO
Project description:Naïve pluripotent stem cells (nPSCs) correspond to nascent epiblast in the pre-implantation embryo. nPSCs from mouse and human differ in self-renewal requirements and potency for trophectoderm generation. Here we investigated chimpanzee (Pan troglodytes) nPSCs. Naïve type colonies emerged after resetting or reprogramming but failed to expand. We found that the block to self-renewal is overcome by inhibition of EZH2, the enzymatic component of Polycomb repressor group 2 (PRC2). Chimpanzee nPSCs are euploid, produce teratomas, and can be capacitated for somatic lineage differentiation in vitro. They show transcriptome relatedness to human nPSCs and early epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee nPSCs differentiate to trophectoderm and form tri-lineage blastoids. We confirmed that PRC2 suppresses self-renewal by genetic deletions. Furthermore, we demonstrate that EZH2 inhibition facilitates feeder-free propagation of human nPSCs. In summary, chimpanzee nPSCs expand the repertoire of systems for studying primate pluripotency and early embryogenesis.
2025-02-26 | GSE278810 | GEO
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:Human pluripotent cell lines were derived from blastocyst-stage embryos and propagated in self-renewal conditions that maintain features of naive pluripotency characteristic of mouse embryonic stem cells. Genome-wide DNA methylation status of HNES1 and HNES3 naive and primed cells was assessed with post-bisulfite adapter tagging (PBAT).
2016-03-01 | E-MTAB-4462 | biostudies-arrayexpress
Project description:Human pluripotent cell lines were derived from blastocyst-stage embryos and propagated in self-renewal conditions that maintain features of naive pluripotency characteristic of mouse embryonic stem cells. Genomic integrity of the HNES1 cell line was assessed with the Affymetrix CytoScan 750K array.
2016-03-01 | E-MTAB-4463 | biostudies-arrayexpress
Project description:Human pluripotent cell lines were derived from blastocyst-stage embryos and propagated in self-renewal conditions that maintain features of naive pluripotency characteristic of mouse embryonic stem cells. Transcriptional activity of HNES1, HNES2 and HNES3 cell lines was assessed with RNA-seq.
2016-03-01 | E-MTAB-4461 | biostudies-arrayexpress
Project description:Pluripotent stem cells are defined by their self-renewal capacity, which is the ability of the stem cells to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into any somatic cell lineage. However, understanding the mechanisms that control stem cell fitness versus the pluripotent cell identity is challenging. To investigate the interplay between these two aspects of pluripotency, we performed four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSC self-renewal conditions, and the dissolution of the primed pluripotency identity during early differentiation. Comparative analyses led to the discovery of genes with distinct roles in pluripotency regulation, including mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control pluripotent identity during early differentiation. We further discovered a core set of factors that control both stem cell fitness and pluripotent identity, including a network of chromatin factors that safeguard pluripotency. Our unbiased and systematic screening and comparative analyses disentangle two interconnected aspects of pluripotency, provide rich datasets for exploring pluripotent cell identity versus cell fitness, and offer a valuable model for categorizing gene function in broad biological contexts.
2024-09-05 | PXD055592 | Pride