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; Tao Cheng

doi:10.1038/ncomms3174

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, Tao Cheng^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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 p21^Cdkn1a (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.

Original language	English (US)
Article number	2174
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3174
State	Published - 2013

Funding

This work was supported by the research grants from MOST (2011CB964801, 2010CB945204, 2011ZX09102-010-04, and 2012CB966604), NIH (AI080424 and HL070561 to T.C.; CA102011 and CA130966 to SYC) and NSFC (81090410, 30825017, 81270595, 81130074 and 90913018). T.C. was a recipient of the Scholar Award from the Leukemia & Lymphoma Society (1027-08). We thank Drs. Daohong Zhou, Jian Yu and Wei Dai for their insightful comments and Dr Paulina Liang for her editorial assistance on this manuscript.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms3174

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title = "The p53-PUMA axis suppresses iPSC generation",

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.",

author = "Yanxin Li and Haizhong Feng and Haihui Gu and Lewis, {Dale W.} and Youzhong Yuan and Lei Zhang and Hui Yu and Peng Zhang and Haizi Cheng and Weimin Miao and Weiping Yuan and Cheng, {Shi Yuan} and Gollin, {Susanne M.} and Tao Cheng",

note = "Funding Information: This work was supported by the research grants from MOST (2011CB964801, 2010CB945204, 2011ZX09102-010-04, and 2012CB966604), NIH (AI080424 and HL070561 to T.C.; CA102011 and CA130966 to SYC) and NSFC (81090410, 30825017, 81270595, 81130074 and 90913018). T.C. was a recipient of the Scholar Award from the Leukemia & Lymphoma Society (1027-08). We thank Drs. Daohong Zhou, Jian Yu and Wei Dai for their insightful comments and Dr Paulina Liang for her editorial assistance on this manuscript.",

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AU - Feng, Haizhong

AU - Gu, Haihui

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AU - Zhang, Lei

AU - Yu, Hui

AU - Zhang, Peng

AU - Cheng, Haizi

AU - Miao, Weimin

AU - Yuan, Weiping

AU - Cheng, Shi Yuan

AU - Gollin, Susanne M.

AU - Cheng, Tao

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PY - 2013

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N2 - 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.

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The p53-PUMA axis suppresses iPSC generation

Abstract

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ASJC Scopus subject areas

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