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Senescence impairs successful reprogramming to pluripotent stem cells

Ana Banito, S. Tamir Rashid, Juan Carlos Acosta, SiDe Li, Carlos‐Filipe Pereira, Imbisaat Geti, Sandra Pinho, José Silva, Véronique Azuara, Martin J. Walsh, Ludovic Vallier, Jesús Gil

Genes & Development · 2009 · ▲ 633 citations

Genomic instability Epigenetic alterations Cellular senescence Stem-cell exhaustion Partial reprogramming (OSK)

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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, 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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Provenance

Source: OpenAlex
DOI: 10.1101/gad.1811609
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Fetched: 2026-07-17 MST

Cite this

APA

Banito, A., Rashid, S.T., Acosta, J.C., Li, S., Pereira, C., Geti, I., Pinho, S., Silva, J., Azuara, V., Walsh, M.J., Vallier, L., & Gil, J. (2009). Senescence impairs successful reprogramming to pluripotent stem cells. <em>Genes & Development</em>. https://doi.org/10.1101/gad.1811609

Vancouver

Banito A, Rashid ST, Acosta JC, Li S, Pereira C, Geti I, et al. Senescence impairs successful reprogramming to pluripotent stem cells. Genes & Development. 2009. doi:10.1101/gad.1811609.

BibTeX

@unpublished{ana2009Senesc, title = {Senescence impairs successful reprogramming to pluripotent stem cells}, author = {Ana Banito and S. Tamir Rashid and Juan Carlos Acosta and SiDe Li and Carlos‐Filipe Pereira and Imbisaat Geti and Sandra Pinho and José Silva and Véronique Azuara and Martin J. Walsh and Ludovic Vallier and Jesús Gil}, journal = {Genes & Development}, year = {2009}, doi = {10.1101/gad.1811609}, }