Int J Biol Sci 2023; 19(3):916-935. doi:10.7150/ijbs.79095 This issue Cite

Research Paper

ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway

Shasha Li1,2,4#, Hui Liu3#, Weidong Liu1,2,4, Ning Shi1,2,5, Ming Zhao1,4, Siyi Wanggou1,6, Weiren Luo7, Lei Wang1,2,4, Bin Zhu1,2,4, Xiang Zuo1,2,4, Wen Xie1,2,4, Cong Zhao1,2,4, Yao Zhou1,2,4, Longlong Luo5, Xiang Gao5, Xingjun Jiang1,2,6✉, Caiping Ren1,2,4✉

1. NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
3. National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
4. The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.
5. State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100039, China.
6. Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
7. Cancer Research Institute, Shenzhen Third People's Hospital, the Second Affiliated Hospital of Southern University of Science and technology, Shenzhen, Guangdong 518100 China.
#These authors contributed equally to this work.

Citation:
Li S, Liu H, Liu W, Shi N, Zhao M, Wanggou S, Luo W, Wang L, Zhu B, Zuo X, Xie W, Zhao C, Zhou Y, Luo L, Gao X, Jiang X, Ren C. ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway. Int J Biol Sci 2023; 19(3):916-935. doi:10.7150/ijbs.79095. https://www.ijbs.com/v19p0916.htm
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Abstract

Graphic abstract

The mechanisms of self-renewal and pluripotency maintenance of human pluripotent stem cells (hPSCs) have not been fully elucidated, especially for the role of those poorly characterized long noncoding RNAs (lncRNAs). ESRG is a lncRNA highly expressed in hPSCs, and its functional roles are being extensively explored in the field. Here, we identified that the transcription of ESRG can be directly regulated by OCT4, a key self-renewal factor in hPSCs. 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 location, safeguarding error-free DNA replication. Further study showed that ESRG knockdown leads to MCM2 abnormalities, resulting in DNA damage and activation of the p53 pathway, ultimately impairs hPSC self-renewal and pluripotency, and induces cell apoptosis. In summary, our study suggests that ESRG, as a novel target of OCT4, plays an essential role in maintaining the cell survival and self-renewal/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 by lncRNAs.

Keywords: ESRG, human pluripotent stem cells, pluripotency, cell survival, OCT4, MCM2, p53


Citation styles

APA
Li, S., Liu, H., Liu, W., Shi, N., Zhao, M., Wanggou, S., Luo, W., Wang, L., Zhu, B., Zuo, X., Xie, W., Zhao, C., Zhou, Y., Luo, L., Gao, X., Jiang, X., Ren, C. (2023). ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway. International Journal of Biological Sciences, 19(3), 916-935. https://doi.org/10.7150/ijbs.79095.

ACS
Li, S.; Liu, H.; Liu, W.; Shi, N.; Zhao, M.; Wanggou, S.; Luo, W.; Wang, L.; Zhu, B.; Zuo, X.; Xie, W.; Zhao, C.; Zhou, Y.; Luo, L.; Gao, X.; Jiang, X.; Ren, C. ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway. Int. J. Biol. Sci. 2023, 19 (3), 916-935. DOI: 10.7150/ijbs.79095.

NLM
Li S, Liu H, Liu W, Shi N, Zhao M, Wanggou S, Luo W, Wang L, Zhu B, Zuo X, Xie W, Zhao C, Zhou Y, Luo L, Gao X, Jiang X, Ren C. ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway. Int J Biol Sci 2023; 19(3):916-935. doi:10.7150/ijbs.79095. https://www.ijbs.com/v19p0916.htm

CSE
Li S, Liu H, Liu W, Shi N, Zhao M, Wanggou S, Luo W, Wang L, Zhu B, Zuo X, Xie W, Zhao C, Zhou Y, Luo L, Gao X, Jiang X, Ren C. 2023. ESRG is critical to maintain the cell survival and self-renewal/pluripotency of hPSCs by collaborating with MCM2 to suppress p53 pathway. Int J Biol Sci. 19(3):916-935.

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