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.
authors.affiliation: Cell Proliferation Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London W12 0NN, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Banito
authors.forename: Sheikh T
authors.initials: ST
authors.lastname: Rashid
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Acosta
authors.forename: SiDe
authors.initials: S
authors.lastname: Li
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Pereira
authors.forename: Imbisaat
authors.initials: I
authors.lastname: Geti
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinho
authors.forename: Jose C
authors.initials: JC
authors.lastname: Silva
authors.forename: Veronique
authors.initials: V
authors.lastname: Azuara
authors.forename: Martin
authors.initials: M
authors.lastname: Walsh
authors.forename: Ludovic
authors.initials: L
authors.lastname: Vallier
authors.forename: Jesús
authors.initials: J
authors.lastname: Gil
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D065150:Cellular Reprogramming; D016922:Cellular Senescence / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D000090062:Kruppel-Like Factor 4; D039904:Pluripotent Stem Cells / Q000166:cytology*
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