Shouhai Wu
Bo Li
Yang Xu
Jingfeng Liu
1 The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China;
2 Center for Regenerative and Translational Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510632, China;
3 Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China;
4 Cancer Research Institute, Guangdong Provincial Key Laboratory of Tumor Immunotherapy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
Funds: This work was supported by the National Natural Science Foundation of China (Grant Nos. 815300045, 81871197, 81930084, 81430032, U1601222), the National High Technology Research and Development Program (863 Program) (No. 2015AA020310), Development and Reform Commission of Shenzhen Municipality (S2016004730009), Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06S638), and Shenzhen "Sanming" Project of Medicine (SZSM201602102).
Received Date: 2019-07-02
Rev Recd Date:2019-08-29
Publish Date:2020-01-10
Abstract
Abstract
Pluripotent stem cells (PSCs) are capable of unlimited self-renewal in culture and differentiation into all functional cell types in the body, and thus hold great promise for regenerative medicine. To achieve their clinical potential, it is critical for PSCs to maintain genomic stability during the extended proliferation. The critical tumor suppressor p53 is required to maintain genomic stability of mammalian cells. In response to DNA damage or oncogenic stress, p53 plays multiple roles in maintaining genomic stability of somatic cells by inducing cell cycle arrest, apoptosis, and senescence to prevent the passage of genetic mutations to the daughter cells. p53 is also required to maintain the genomic stability of PSCs. However, in response to the genotoxic stresses, a primary role of p53 in PSCs is to induce the differentiation of PSCs and inhibit pluripotency, providing mechanisms to maintain the genomic stability of the self-renewing PSCs. In addition, the roles of p53 in cellular metabolism might also contribute to genomic stability of PSCs by limiting oxidative stress. In summary, the elucidation of the roles of p53 in PSCs will be a prerequisite for developing safe PSC-based cell therapy.Keywords: p53,
embryonic stem cells,
induced pluripotent stem cells,
genetic stability,
metabolism
PDF全文下载地址:
http://www.protein-cell.org/article/exportPdf?id=1590f23c-1ad8-4523-9e4a-c7cf82c1a7a9&language=en
