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- Title
Pten-mediated Gsk3β modulates the naïve pluripotency maintenance in embryonic stem cells.
- Authors
Wang, Wuming; Lu, Gang; Su, Xianwei; Tang, Chengcheng; Li, Hongjian; Xiong, Zhiqiang; Leung, Chi-Kwan; Wong, Man-Sze; Liu, Hongbin; Ma, Jin-Long; Cheung, Hoi-Hung; Kung, Hsiang-Fu; Chen, Zi-Jiang; Chan, Wai-Yee
- Abstract
Mouse embryonic stem cells (ESCs) are isolated from the inner cell mass of blastocysts, and they exist in different states of pluripotency—naïve 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 naïve pluripotency by blocking Gsk3β 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 Gsk3β modulates the naïve pluripotency of ESCs and that Pten ablation regulates the lineage-specific differentiation.
- Publication
Cell Death & Disease, 2020, Vol 11, Issue 2, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-020-2271-0