1. Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau SAR, China. 2. Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, RTP, NC 27709, USA. 3. Animal Research Core Facility, Faculty of Health Sciences, University of Macau, Macau SAR, China. 4. Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, China. 5. Bioimaging and Stem Cell Core Facility, Faculty of Health Sciences, University of Macau, Macau SAR, China. 6. MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, China.
✉ Corresponding author: Guokai Chen, Ph.D., Faculty of Health Sciences, University of Macau, E12-3060, Taipa, Macau SAR, 999078. Phone: (853)-8822 4985; Fax: (853)-8822 2314; Email: guokaichenedu.mo.
Citation:
Zhou X, Ren Z, Xu J, Deng C, Zhang Z, Godoy-Parejo C, Xu F, Huang ECC, Wang J, Cai Z, Liu W, Hu G, Chen G. Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency. Int J Biol Sci 2022; 18(9):3562-3575. doi:10.7150/ijbs.71199. https://www.ijbs.com/v18p3562.htm
Insulin is essential for diverse biological processes in human pluripotent stem cells (hPSCs). However, the underlying mechanism of insulin's multitasking ability remains largely unknown. Here, we show that insulin controls hPSC survival and proliferation by modulating RNA translation via distinct pathways. It activates AKT signaling to inhibit RNA translation of pro-apoptotic proteins such as NOXA/PMAIP1, thereby promoting hPSC survival. At the same time, insulin acts via the mTOR pathway to enhance another set of RNA translation for cell proliferation. Consistently, mTOR inhibition by rapamycin results in eIF4E phosphorylation and translational repression. It leads to a dormant state with sustained pluripotency but reduced cell growth. Together, our study uncovered multifaceted regulation by insulin in hPSC survival and proliferation, and highlighted RNA translation as a key step to mediate mitogenic regulation in hPSCs.
Zhou, X., Ren, Z., Xu, J., Deng, C., Zhang, Z., Godoy-Parejo, C., Xu, F., Huang, E.C.C., Wang, J., Cai, Z., Liu, W., Hu, G., Chen, G. (2022). Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency. International Journal of Biological Sciences, 18(9), 3562-3575. https://doi.org/10.7150/ijbs.71199.
ACS
Zhou, X.; Ren, Z.; Xu, J.; Deng, C.; Zhang, Z.; Godoy-Parejo, C.; Xu, F.; Huang, E.C.C.; Wang, J.; Cai, Z.; Liu, W.; Hu, G.; Chen, G. Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency. Int. J. Biol. Sci. 2022, 18 (9), 3562-3575. DOI: 10.7150/ijbs.71199.
NLM
Zhou X, Ren Z, Xu J, Deng C, Zhang Z, Godoy-Parejo C, Xu F, Huang ECC, Wang J, Cai Z, Liu W, Hu G, Chen G. Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency. Int J Biol Sci 2022; 18(9):3562-3575. doi:10.7150/ijbs.71199. https://www.ijbs.com/v18p3562.htm
CSE
Zhou X, Ren Z, Xu J, Deng C, Zhang Z, Godoy-Parejo C, Xu F, Huang ECC, Wang J, Cai Z, Liu W, Hu G, Chen G. 2022. Insulin Directs Dichotomous Translational Regulation to Control Human Pluripotent Stem Cell Survival, Proliferation and Pluripotency. Int J Biol Sci. 18(9):3562-3575.
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