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Genes Dev. 2009 Sep 15;23(18):2134-9. doi: 10.1101/gad.1811609. Epub 2009 Aug 20.

Senescence impairs successful reprogramming to pluripotent stem cells.

Author information

  • 1Cell Proliferation Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London W12 0NN, United Kingdom.

Abstract

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by overexpressing combinations of factors such as Oct4, Sox2, Klf4, and c-Myc. Reprogramming is slow and stochastic, suggesting the existence of barriers limiting its efficiency. Here we identify senescence as one such barrier. Expression of the four reprogramming factors triggers senescence by up-regulating p53, p16(INK4a), and p21(CIP1). Induction of DNA damage response and chromatin remodeling of the INK4a/ARF locus are two of the mechanisms behind senescence induction. Crucially, ablation of different senescence effectors improves the efficiency of reprogramming, suggesting novel strategies for maximizing the generation of iPS cells.

PMID:
19696146
[PubMed - indexed for MEDLINE]
PMCID:
PMC2751980
Free PMC Article

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