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Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle
Ist Teil von
Cell stem cell, 2017-03, Vol.20 (3), p.407-414.e4
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2017
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
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.
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•Tissue damage enables in vivo OSKM-mediated reprogramming in skeletal muscle•Satellite cells are a major cell of origin for in vivo reprogramming in muscle•Accumulation of senescent cells after injury or in aging promotes reprogramming•IL-6 release from senescent cells positively stimulates in vivo reprogramming
Li and colleagues reported that tissue damage enables in vivo reprogramming in skeletal muscle, which can arise from muscle stem cells. They also show that damage-induced cellular senescence promotes cellular plasticity through release of secreted proteins, including IL-6. Their findings could have implications for developing therapeutic lineage reprogramming strategies.