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Cell Stem Cell. 2017 Mar 2;20(3):407-414.e4. doi: 10.1016/j.stem.2016.11.020. Epub 2016 Dec 22.

Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle.

Author information

1
Cellular Plasticity & Disease Modelling, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France; CNRS, UMR3738, Rue du Dr Roux, Paris 75015, France.
2
Stem Cells & Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
3
Stem Cells & Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France; CNRS, UMR3738, Rue du Dr Roux, Paris 75015, France.
4
Cellular Plasticity & Disease Modelling, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
5
Human Histopathology and Animal Models, Department of Infection & Epidemiology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
6
Stem Cells & Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France; CNRS, UMR3738, Rue du Dr Roux, Paris 75015, France. Electronic address: shahragim.tajbakhsh@pasteur.fr.
7
Cellular Plasticity & Disease Modelling, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France; CNRS, UMR3738, Rue du Dr Roux, Paris 75015, France. Electronic address: han.li@pasteur.fr.

Abstract

In vivo reprogramming is a promising approach for tissue regeneration in response to injury. Several examples of in vivo reprogramming have been reported in a variety of lineages, but some including skeletal muscle have so far proven refractory. Here, we show that acute and chronic injury enables transcription-factor-mediated reprogramming in skeletal muscle. Lineage tracing indicates that this response frequently originates from Pax7+ muscle stem cells. Injury is associated with accumulation of senescent cells, and advanced aging or local irradiation further enhanced in vivo reprogramming, while selective elimination of senescent cells reduced reprogramming efficiency. The effect of senescence appears to be, at least in part, due to the release of interleukin 6 (IL-6), suggesting a potential link with the senescence-associated secretory phenotype. Collectively, our findings highlight a beneficial paracrine effect of injury-induced senescence on cellular plasticity, which will be important for devising strategies for reprogramming-based tissue repair.

KEYWORDS:

IL-6; aging; cellular plasticity; cellular senescence; in vivo reprogramming; pluripotency; regeneration; skeletal muscle

PMID:
28017795
DOI:
10.1016/j.stem.2016.11.020
[Indexed for MEDLINE]
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