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Senescence impairs successful reprogramming to pluripotent stem cells

Banito, Ana; Rashid, Sheikh T.; Acosta, Juan Carlos; Li, Si De; Pereira, Carlos F. LU ; Geti, Imbisaat; Pinho, Sandra; Silva, Jose C. LU ; Azuara, Veronique and Walsh, Martin, et al. (2009) In Genes and Development 23(18). p.2134-2139
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.

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publishing date
type
Contribution to journal
publication status
published
keywords
iPS, miR-302, p21, Reprogramming, Senescence, Sox2
in
Genes and Development
volume
23
issue
18
pages
6 pages
publisher
Cold Spring Harbor Laboratory Press
external identifiers
  • scopus:70349093119
ISSN
0890-9369
DOI
10.1101/gad.1811609
language
English
LU publication?
no
id
1dfbf8f7-b374-443d-aa01-9ea62373c823
date added to LUP
2017-10-02 17:32:00
date last changed
2017-10-29 05:06:53
@article{1dfbf8f7-b374-443d-aa01-9ea62373c823,
  abstract     = {<p>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<sup>INK4a</sup>, and p21<sup>CIP1</sup>. 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.</p>},
  author       = {Banito, Ana and Rashid, Sheikh T. and Acosta, Juan Carlos and Li, Si De and Pereira, Carlos F. and Geti, Imbisaat and Pinho, Sandra and Silva, Jose C. and Azuara, Veronique and Walsh, Martin and Vallier, Ludovic and Gil, Jesús},
  issn         = {0890-9369},
  keyword      = {iPS,miR-302,p21,Reprogramming,Senescence,Sox2},
  language     = {eng},
  month        = {09},
  number       = {18},
  pages        = {2134--2139},
  publisher    = {Cold Spring Harbor Laboratory Press},
  series       = {Genes and Development},
  title        = {Senescence impairs successful reprogramming to pluripotent stem cells},
  url          = {http://dx.doi.org/10.1101/gad.1811609},
  volume       = {23},
  year         = {2009},
}