诱导多能干细胞
表观遗传学
外胚层
生物
电容
DNA甲基化
重编程
胚胎干细胞
细胞生物学
遗传学
基因
基因表达
精子
原肠化
作者
João Agostinho de Sousa,Chee Wai Wong,Ilona Dunkel,Thomas Owens,Philipp Voigt,Adam Hodgson,Duncan Baker,Edda G. Schulz,Wolf Reik,Austin Smith,Maria Rostovskaya,Ferdinand von Meyenn
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-09-29
卷期号:9 (39)
标识
DOI:10.1126/sciadv.adg1936
摘要
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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