The p53–PUMA axis suppresses iPSC generation

Yanxin Li, Haizhong Feng, Haihui Gu, Dale W. Lewis, Youzhong Yuan, Lei Zhang, Hui Yu, Peng Zhang, Haizi Cheng, Weimin Miao, Weiping Yuan, Shi-Yuan Cheng, Susanne M. Gollin and Tao Cheng ()
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Yanxin Li: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College
Haizhong Feng: Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Haihui Gu: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College
Dale W. Lewis: University of Pittsburgh Graduate School of Public Health
Youzhong Yuan: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Lei Zhang: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College
Hui Yu: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Peng Zhang: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Haizi Cheng: University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute
Weimin Miao: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College
Weiping Yuan: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College
Shi-Yuan Cheng: Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine
Susanne M. Gollin: University of Pittsburgh Graduate School of Public Health
Tao Cheng: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract Mechanisms underlying the reprogramming process of induced pluripotent stem cells remain poorly defined. Like tumorigenesis, generation of induced pluripotent stem cells was shown to be suppressed by the Trp53 (p53) pathway, at least in part via p21Cdkn1a (p21)-mediated cell cycle arrest. Here we examine the role of PUMA, a pro-apoptotic mediator of p53, during somatic reprogramming in comparison to p21 in the p53 pathway. Using mouse strains deficient in these molecules, we demonstrate that PUMA is an independent mediator of the negative effect of p53 on induced pluripotent stem cell induction. PUMA deficiency leads to a better survival rate associated with reduced DNA damage and fewer chromosomal aberrations in induced pluripotent stem cells, whereas loss of p21 or p53 results in an opposite outcome. Given these new findings, PUMA may serve as a distinct and more desirable target in the p53 pathway for induced pluripotent stem cell generation, thereby having important implications for potential therapeutic applications of induced pluripotent stem cells.

Date: 2013
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DOI: 10.1038/ncomms3174

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