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Epigenetic dynamics during capacitation of naïve human pluripotent stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218512 | GEO | 2023/10/03

REPOSITORIES: GEO

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Epigenetic dynamics during capacitation of naive human pluripotent stem cells.

Project description:Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine. Naïve hPSCs hold promise to overcome some of the limitations of conventional (primed) hPSCs, including recurrent epigenetic anomalies. Naïve-to-primed transition (capacitation) follows transcriptional dynamics of human embryonic epiblast and is necessary for somatic differentiation from naïve hPSCs. We found that capacitated hPSCs are transcriptionally closer to postimplantation epiblast than conventional hPSCs. This prompted us to comprehensively study epigenetic and related transcriptional changes during capacitation. Our results show that CpG islands, gene regulatory elements, and retrotransposons are hotspots of epigenetic dynamics during capacitation and indicate possible distinct roles of specific epigenetic modifications in gene expression control between naïve and primed hPSCs. Unexpectedly, PRC2 activity appeared to be dispensable for the capacitation. We find that capacitated hPSCs acquire an epigenetic state similar to conventional hPSCs. Significantly, however, the X chromosome erosion frequently observed in conventional female hPSCs is reversed by resetting and subsequent capacitation.

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Epigenetic dynamics during capacitation of naïve human pluripotent stem cells [PBAT]

Project description:Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine and the primary source for many novel cellular therapies. The development of naïve culture conditions has led to the expectation that these naïve hPSCs could overcome some of the limitations found in conventional (primed) hPSCs culture conditions, including recurrent epigenetic anomalies. Recent work has shown that transition to the primed state (or capacitation) is necessary for naïve hPSCs to acquire multi-lineage differentiation competence. This pluripotent state transition may recapitulate essential features of human peri-implantation development. Here we studied epigenetic changes during the transition between naïve and primed pluripotency, examining global genomic redistribution of histone modifications, chromatin accessibility, and DNA methylation, and correlating these with gene expression. We identify CpG islands, enhancers, and retrotransposons as hotspots of epigenetic dynamics between pluripotency states. Our results further reveal that hPSC resetting and subsequent capacitation rescue X chromosome-linked epigenetic erosion and reduce the ectoderm-biased gene expression of conventional primed hPSCs.

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Epigenetic dynamics during capacitation of naïve human pluripotent stem cells

Project description:Epigenetic dynamics during capacitation of naïve human pluripotent stem cells

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