Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.
Science
; 354(6315)2016 11 25.
Article
en En
| MEDLINE
| ID: mdl-27884981
ABSTRACT
Reprogramming of differentiated cells into pluripotent cells can occur in vivo, but the mechanisms involved remain to be elucidated. Senescence is a cellular response to damage, characterized by abundant production of cytokines and other secreted factors that, together with the recruitment of inflammatory cells, result in tissue remodeling. Here, we show that in vivo expression of the reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to senescence and reprogramming, both coexisting in close proximity. Genetic and pharmacological analyses indicate that OSKM-induced senescence requires the Ink4a/Arf locus and, through the production of the cytokine interleukin-6, creates a permissive tissue environment for in vivo reprogramming. Biological conditions linked to senescence, such as tissue injury or aging, favor in vivo reprogramming by OSKM. These observations may be relevant for tissue repair.
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Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Senescencia Celular
/
Inhibidor p16 de la Quinasa Dependiente de Ciclina
/
Reprogramación Celular
/
Células Madre Pluripotentes Inducidas
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2016
Tipo del documento:
Article
País de afiliación:
España