Senescence impairs successful reprogramming to pluripotent stem cells

Ana Banito, Sheikh T Rashid, Juan Carlos Acosta, SiDe Li, Carlos F Pereira, Imbisaat Geti, Sandra Pinho, Jose C Silva, Veronique Azuara, Martin Walsh, Ludovic Vallier, Jesús Gil

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)2134-2139
Number of pages6
JournalGenes & Development
Volume23
Issue number18
DOIs
Publication statusPublished - 15 Sep 2009

Keywords

  • Pluripotent Stem Cells
  • Animals
  • Cell Aging
  • Humans
  • Cell Differentiation
  • Gene Expression Regulation
  • Nuclear Reprogramming
  • Cell Line
  • p21CIP1
  • Sox2
  • miR-302

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