Embryonic stem cell related gene regulates alternative splicing of transcription factor 3 to maintain human embryonic stem cells' self-renewal and pluripotency.

Autor:	Xie W; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; 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, 410078, People's Republic of China., Liu W; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; 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, 410078, People's Republic of China., Wang L; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; 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, 410078, People's Republic of China., Li S; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China., Liao Z; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; 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, 410078, People's Republic of China., Xu H; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; NHC Key Laboratory of Biological Nanotechnology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China., Li Y; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; 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, 410078, People's Republic of China., Jiang X; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China., Ren C; NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.; 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, 410078, People's Republic of China.
Jazyk:	angličtina
Zdroj:	Stem cells (Dayton, Ohio) [Stem Cells] 2024 Jun 14; Vol. 42 (6), pp. 540-553.
DOI:	10.1093/stmcls/sxae020
Abstrakt:	Exploring the mechanism of self-renewal and pluripotency maintenance of human embryonic stem cells (hESCs) is of great significance in basic research and clinical applications, but it has not been fully elucidated. Long non-coding RNAs (lncRNAs) have been shown to play a key role in the self-renewal and pluripotency maintenance of hESCs. We previously reported that the lncRNA ESRG, which is highly expressed in undifferentiated hESCs, can maintain the self-renewal and pluripotency of hPSCs. RNA pull-down mass spectrometry showed that ESRG could bind to other proteins, among which heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) attracted our attention. In this study, we showed that HNRNPA1 can maintain self-renewal and pluripotency of hESCs. ESRG bound to and stabilized HNRNPA1 protein through the ubiquitin-proteasome pathway. In addition, knockdown of ESRG or HNRNPA1 resulted in alternative splicing of TCF3, which originally and primarily encoded E12, to mainly encode E47 and inhibit CDH1 expression. HNRNPA1 could rescue the biological function changes of hESCs caused by ESRG knockdown or overexpression. Our results suggest that ESRG regulates the alternative splicing of TCF3 to affect CDH1 expression and maintain hESCs self-renewal and pluripotency by binding and stabilizing HNRNPA1 protein. This study lays a good foundation for exploring the new molecular regulatory mechanism by which ESRG maintains hESCs self-renewal and pluripotency. (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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