Expanded Potential Stem Cells from Human Embryos Have an Open Chromatin Configuration with Enhanced Trophoblast Differentiation Ability

Autor: Andy Chun Hang Chen, Yin Lau Lee, Hanzhang Ruan, Wen Huang, Sze Wan Fong, Siyu Tian, Kai Chuen Lee, Genie Minju Wu, Yongqi Tan, Timothy Chun Hin Wong, Jian Wu, Weiyu Zhang, Dandan Cao, Judy Fung Cheung Chow, Pengtao Liu, William Shu Biu Yeung
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Advanced Science, Vol 10, Iss 11, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202204797
Popis: Abstract Human expanded potential stem cells (hEPSC) have been derived from human embryonic stem cells and induced pluripotent stem cells. Here direct derivation of hEPSC from human pre‐implantation embryos is reported. Like the reported hEPSC, the embryo‐derived hEPSC (hEPSC‐em) exhibit a transcriptome similar to morula, comparable differentiation potency, and high genome editing efficiency. Interestingly, the hEPSC‐em show a unique H3 lysine‐4 trimethylation (H3K4me3) open chromatin conformation; they possess a higher proportion of H3K4me3 bound broad domain (>5 kb) than the reported hEPSC, naive, and primed embryonic stem cells. The open conformation is associated with enhanced trophoblast differentiation potency with increased trophoblast gene expression upon induction of differentiation and success in derivation of trophoblast stem cells with bona fide characteristics. Hippo signaling is specifically enriched in the H3K4me3 broad domains of the hEPSC‐. Knockout of the Hippo signaling gene, YAP1 abolishes the ability of the embryo‐derived EPSC to form trophoblast stem cells.
Databáze: Directory of Open Access Journals
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