Central South University - National Clinical Research Center for Geriatric Disorders; Central South University - Department of Neurosurgery, Xiangya Hospital
Central South University - National Clinical Research Center for Geriatric Disorders; Central South University - Cancer Research Institute, Department of Neurosurgery
The mechanisms of self-renewal and pluripotency maintenance of human pluripotent stem cells (hPSCs) have not been fully elucidated. Here, we identified that the transcription of ESRG, a long non-coding RNA highly expressed in hPSCs which was first cloned by us, is directly regulated by OCT4. Knockdown of ESRG induces hPSC differentiation, cell cycle arrest, and apoptosis. ESRG binds to MCM2, a replication-licensing factor, to sustain its steady-state level and nuclear translocation, safeguarding error-free DNA replication. Further study showed that ESRG knockdown leads to MCM2 abnormality, resulting in DNA damage and activation of p53 pathway, ultimately deregulates hPSC self-renewal and pluripotency. In sum, our research suggests that ESRG, as a novel target of OCT4, plays an essential role in maintaining the self-renewal and pluripotency of hPSCs in collaboration with MCM2 to suppress p53 signaling. These findings provide critical insights into the mechanisms underlying the maintenance of self-renewal and pluripotency in hPSCs.
Li, Shasha and Liu, Hui and Zhu, Hecheng and Luo, Longlong and Zhao, Ming and Wanggou, Siyi and Luo, Weiren and Zhao, Ming and Liu, Weidong and Wang, Lei and Zhu, Bin and Zuo, Xiang and Xie, Wen and Zhao, Cong and Zhou, Yao and Jiang, Xingjun and Ren, Caiping, ESRG, a Novel Target of OCT4, Maintains Self-Renewal and Pluripotency of Human Pluripotent Stem Cells in Collaboration With MCM2. Available at SSRN: https://ssrn.com/abstract=4035887 or http://dx.doi.org/10.2139/ssrn.4035887
This version of the paper has not been formally peer reviewed.
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