Senescence impairs successful reprogramming to pluripotent stem cells

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

doi:10.1101/gad.1811609

Senescence impairs successful reprogramming to pluripotent stem cells

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

Research output: Contribution to journal › Article › peer-review

514 Scopus citations

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 language	English (US)
Pages (from-to)	2134-2139
Number of pages	6
Journal	Genes and Development
Volume	23
Issue number	18
DOIs	https://doi.org/10.1101/gad.1811609
State	Published - Sep 15 2009
Externally published	Yes

Keywords

Reprogramming
Senescence
Sox2
iPS
miR-302
p21

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.1811609

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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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AU - Banito, Ana

AU - Rashid, Sheikh T.

AU - Acosta, Juan Carlos

AU - Li, Si De

AU - Pereira, Carlos F.

AU - Geti, Imbisaat

AU - Pinho, Sandra

AU - Silva, Jose C.

AU - Azuara, Veronique

AU - Walsh, Martin

AU - Vallier, Ludovic

AU - Gil, Jesús

PY - 2009/9/15

Y1 - 2009/9/15

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AB - 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.

KW - Reprogramming

KW - Senescence

KW - Sox2

KW - iPS

KW - miR-302

KW - p21

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Senescence impairs successful reprogramming to pluripotent stem cells

Abstract

Keywords

ASJC Scopus subject areas

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