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

Research output: Contribution to journalArticlepeer-review

39 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 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.

Original languageEnglish (US)
Article number2174
JournalNature communications
Volume4
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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