Senescence impairs successful reprogramming to pluripotent stem cells
(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.
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1dfbf8f7-b374-443d-aa01-9ea62373c823
- author
- publishing date
- 2009-09-15
- 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 (CSHL)
- external identifiers
-
- pmid:19696146
- 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
- 2024-09-17 08:55:57
@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}}, keywords = {{iPS; miR-302; p21; Reprogramming; Senescence; Sox2}}, language = {{eng}}, month = {{09}}, number = {{18}}, pages = {{2134--2139}}, publisher = {{Cold Spring Harbor Laboratory Press (CSHL)}}, series = {{Genes and Development}}, title = {{Senescence impairs successful reprogramming to pluripotent stem cells}}, url = {{http://dx.doi.org/10.1101/gad.1811609}}, doi = {{10.1101/gad.1811609}}, volume = {{23}}, year = {{2009}}, }