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

被引：5

作者：

Chen, Andy Chun Hang ^{[1
,2
,3
]}

Lee, Yin Lau ^{[1
,2
,3
]}

Ruan, Hanzhang ^{[1
]}

Huang, Wen ^{[1
]}

Fong, Sze Wan ^{[1
]}

Tian, Siyu ^{[1
]}

Lee, Kai Chuen ^{[1
,3
]}

Wu, Genie Minju ^{[1
]}

Tan, Yongqi ^{[1
]}

Wong, Timothy Chun Hin ^{[3
]}

Wu, Jian ^{[3
]}

Zhang, Weiyu ^{[3
]}

Cao, Dandan ^{[2
]}

Chow, Judy Fung Cheung ^{[1
]}

Liu, Pengtao ^{[3
,4
]}

Yeung, William Shu Biu ^{[1
,2
,3
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, Sch Clin Med, Dept Obstet & Gynaecol, Hong Kong, Peoples R China

[2] Univ Hong Kong, Shenzhen Hosp, Reprod Med Ctr, Shenzhen Key Lab Fertil Regulat, Shenzhen 518000, Peoples R China

[3] Ctr Translat Stem Cell Biol, Bldg 17 W,Hong Kong Sci & Technol Pk, Hong Kong, Peoples R China

[4] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Stem Cell & Regenerat Med Consortium, Hong Kong, Peoples R China

来源：

ADVANCED SCIENCE | 2023年 / 10卷 / 11期

关键词：

chromatin remodeling; expanded potential stem cells; hippo signaling pathway; trophoblast differentiation; BROAD H3K4ME3; NAIVE; TROPHECTODERM; ESTABLISHMENT; PLURIPOTENCY; DOMAINS; PROTEIN; IDENTIFICATION; MAINTENANCE; REPRESSION;

D O I：

10.1002/advs.202204797

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：18

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