Senescence impairs successful reprogramming to pluripotent stem cells

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

Research output: Contribution to journalArticle

404 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2134-2139
Number of pages6
JournalGenes and Development
Volume23
Issue number18
DOIs
StatePublished - Sep 15 2009
Externally publishedYes

Fingerprint

Pluripotent Stem Cells
Induced Pluripotent Stem Cells
Chromatin Assembly and Disassembly
DNA Damage

Keywords

  • iPS
  • miR-302
  • p21
  • Reprogramming
  • Senescence
  • Sox2

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Banito, A., Rashid, S. T., Acosta, J. C., Li, S., Pereira, C. F., Geti, I., ... Gil, J. (2009). Senescence impairs successful reprogramming to pluripotent stem cells. Genes and Development, 23(18), 2134-2139. https://doi.org/10.1101/gad.1811609

Senescence impairs successful reprogramming to pluripotent stem cells. / Banito, Ana; Rashid, Sheikh T.; Acosta, Juan Carlos; Li, SiDe; Pereira, Carlos F.; Geti, Imbisaat; Pinho, Sandra I.; Silva, Jose C.; Azuara, Veronique; Walsh, Martin; Vallier, Ludovic; Gil, Jesús.

In: Genes and Development, Vol. 23, No. 18, 15.09.2009, p. 2134-2139.

Research output: Contribution to journalArticle

Banito, A, Rashid, ST, Acosta, JC, Li, S, Pereira, CF, Geti, I, Pinho, SI, Silva, JC, Azuara, V, Walsh, M, Vallier, L & Gil, J 2009, 'Senescence impairs successful reprogramming to pluripotent stem cells', Genes and Development, vol. 23, no. 18, pp. 2134-2139. https://doi.org/10.1101/gad.1811609
Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I et al. Senescence impairs successful reprogramming to pluripotent stem cells. Genes and Development. 2009 Sep 15;23(18):2134-2139. https://doi.org/10.1101/gad.1811609
Banito, Ana ; Rashid, Sheikh T. ; Acosta, Juan Carlos ; Li, SiDe ; Pereira, Carlos F. ; Geti, Imbisaat ; Pinho, Sandra I. ; Silva, Jose C. ; Azuara, Veronique ; Walsh, Martin ; Vallier, Ludovic ; Gil, Jesús. / Senescence impairs successful reprogramming to pluripotent stem cells. In: Genes and Development. 2009 ; Vol. 23, No. 18. pp. 2134-2139.
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