Naive Human Embryonic Stem Cells Can Give Rise to Cells with a Trophoblast-like Transcriptome and Methylome

被引：137

作者：

Cinkornpumin, Jessica K. ^{[1
]}

Kwon, Sin Young ^{[1
]}

Guo, Yixin ^{[4
]}

Hossain, Ishtiaque ^{[1
]}

Sirois, Jacinthe ^{[1
,2
]}

Russett, Colleen S. ^{[1
]}

Tseng, Hsin-Wei ^{[1
]}

Okae, Hiroaki ^{[5
]}

Arima, Takahiro ^{[5
]}

Duchaine, Thomas F. ^{[1
,2
]}

Liu, Wanlu ^{[3
,4
]}

Pastor, William A. ^{[1
,2
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[2] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada

[3] Zhejiang Univ, Affiliated Hosp 2, Dept Orthoped, Sch Med, Hangzhou 310029, Peoples R China

[4] Zhejiang Univ, Sch Med, Univ Edinburgh Inst, ZJU UoE Inst, Int Campus,718 East Haizhou Rd, Haining 314400, Peoples R China

[5] Tohoku Univ, Dept Informat Genet, Environm & Genome Res Ctr, Grad Sch Med, Sendai, Miyagi 9808575, Japan

来源：

STEM CELL REPORTS | 2020年 / 15卷 / 01期

基金：

加拿大健康研究院;

关键词：

IN-VITRO; PLURIPOTENCY; DERIVATION; CRITERIA;

D O I：

10.1016/j.stemcr.2020.06.003

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human embryonic stem cells (hESCs) readily differentiate to somatic or germ lineages but have impaired ability to form extra-embryonic lineages such as placenta or yolk sac. Here, we demonstrate that naive hESCs can be converted into cells that exhibit the cellular and molecular phenotypes of human trophoblast stem cells (hTSCs) derived from human placenta or blastocyst. The resulting "transdifferentiated'' hTSCs show reactivation of core placental genes, acquisition of a placenta-like methylome, and the ability to differentiate to extravillous trophoblasts and syncytiotrophoblasts. Modest differences are observed between transdifferentiated and placental hTSCs, most notably in the expression of certain imprinted loci. These results suggest that naive hESCs can differentiate to extra-embryonic lineage and demonstrate a new way of modeling human trophoblast specification and placental methylome establishment.

引用

页码：198 / 213

页数：16

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