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

Wuming Wang, Gang Lu, Xianwei Su, Chengcheng Tang, Hongjian Li, Zhiqiang Xiong, Chi-Kwan Leung, Man-Sze Wong, Hongbin Liu, Jin-Long Ma, Hoi-Hung Cheung, Hsiang-Fu Kung, Zi-Jiang Chen, Wai-Yee Chan

Cell death & disease 2020 Feb 07

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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.

Citation

Wuming Wang, Gang Lu, Xianwei Su, Chengcheng Tang, Hongjian Li, Zhiqiang Xiong, Chi-Kwan Leung, Man-Sze Wong, Hongbin Liu, Jin-Long Ma, Hoi-Hung Cheung, Hsiang-Fu Kung, Zi-Jiang Chen, Wai-Yee Chan. Pten-mediated Gsk3β modulates the naïve pluripotency maintenance in embryonic stem cells. Cell death & disease. 2020 Feb 07;11(2):107