Pten-mediated Gsk3β modulates the naive pluripotency maintenance in embryonic stem cells

被引：11

作者：

Wang, Wuming ^{[1
,2
]}

Lu, Gang ^{[1
,2
]}

Su, Xianwei ^{[1
,2
,3
]}

Tang, Chengcheng ^{[1
]}

Li, Hongjian ^{[1
,2
,3
]}

Xiong, Zhiqiang ^{[2
,3
]}

Leung, Chi-Kwan ^{[1
,2
,3
]}

Wong, Man-Sze ^{[1
,2
]}

Liu, Hongbin ^{[1
,2
]}

Ma, Jin-Long ^{[1
,2
,3
]}

Cheung, Hoi-Hung ^{[1
]}

Kung, Hsiang-Fu ^{[1
,2
]}

Chen, Zi-Jiang ^{[1
,2
,4
]}

Chan, Wai-Yee ^{[1
,2
]}

机构：

[1] Chinese Univ Hong Kong, Sch Biomed Sci, CUHK SDU Joint Lab Reprod Genet, Hong Kong, Peoples R China

[2] Natl Res Ctr Assisted Reprod Technol & Reprod Gen, Jinan 250001, Peoples R China

[3] SDIVF R&D Ctr, Shatin, Hong Kong Sci Pk, Hong Kong, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Ctr Reprod Med, Shanghai 200135, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 02期

基金：

中国国家自然科学基金;

关键词：

SELF-RENEWAL; MOUSE; DIFFERENTIATION; ACTIVATION; AKT; STATE; PHOSPHORYLATION; PROLIFERATION; PHOSPHATASE; INHIBITION;

D O I：

10.1038/s41419-020-2271-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mouse embryonic stem cells (ESCs) are isolated from the inner cell mass of blastocysts, and they exist in different states of pluripotency-naive and primed states. Pten is a well-known tumor suppressor. Here, we generated Pten(-/-) mouse ESCs with the CRISPR-Cas9 system and verified that Pten-/- ESCs maintained naive pluripotency by blocking Gsk3 beta activity. Serum/LIF and 2i (MAPK and GSK3 inhibitors) conditions are commonly used for ESC maintenance. We show that the Pten-inhibitor SF1670 contributed to sustaining mouse ESCs and that Pten activation by the S380A, T382A, and T383A mutations (Pten-A3) suppressed the pluripotency of ESCs. The in vivo teratoma formation ability of SF1670-treated ESCs increased, while the Pten-A3 mutations suppressed teratoma formation. Furthermore, the embryoid bodies derived from Pten-deficient ESCs or SF1670-treated wild- type ESCs showed greater expression of ectoderm and pluripotency markers. These results suggest that Pten-mediated Gsk3 beta modulates the naive pluripotency of ESCs and that Pten ablation regulates the lineage-specific differentiation.

引用

页数：15

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