Senescence impairs successful reprogramming to pluripotent stem cells

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

Imperial College London

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

527 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, 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
Pages (from-to)	2134-9
Number of pages	6
Journal	Genes & development
Volume	23
Issue number	18
Early online date	20 Aug 2009
DOIs	https://doi.org/10.1101/gad.1811609
Publication status	Published - 15 Sept 2009

Keywords

Animals
Cell Differentiation
Cell Line
Cellular Reprogramming
Cellular Senescence
Gene Expression Regulation
Humans
Pluripotent Stem Cells
Journal Article
Research Support, Non-U.S. Gov't

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10.1101/gad.1811609

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title = "Senescence impairs successful reprogramming to pluripotent stem cells",

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.",

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AU - Banito, Ana

AU - Rashid, Sheikh T

AU - Acosta, Juan Carlos

AU - Li, SiDe

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

N2 - 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.

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, 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.

KW - Animals

KW - Cell Differentiation

KW - Cell Line

KW - Cellular Reprogramming

KW - Cellular Senescence

KW - Gene Expression Regulation

KW - Humans

KW - Pluripotent Stem Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1101/gad.1811609

M3 - Article

C2 - 19696146

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VL - 23

SP - 2134

EP - 2139

JO - Genes & development

JF - Genes & development

IS - 18

ER -

Senescence impairs successful reprogramming to pluripotent stem cells

Abstract

Keywords

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