Senescence impairs successful reprogramming to pluripotent stem cells

Research output: Contribution to journalArticle

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, p16INK4a, and p21CIP1. 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.

Details

Authors
  • Ana Banito
  • Sheikh T. Rashid
  • Juan Carlos Acosta
  • Si De Li
  • Carlos F. Pereira
  • Imbisaat Geti
  • Sandra Pinho
  • Jose C. Silva
  • Veronique Azuara
  • Martin Walsh
  • Ludovic Vallier
  • Jesús Gil
External organisations
  • Imperial College London
  • University of Cambridge
  • Icahn School of Medicine at Mount Sinai
Research areas and keywords

Keywords

  • iPS, miR-302, p21, Reprogramming, Senescence, Sox2
Original languageEnglish
Pages (from-to)2134-2139
Number of pages6
JournalGenes and Development
Volume23
Issue number18
Publication statusPublished - 2009 Sep 15
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes