title: Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle.
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.
authors.affiliation: 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.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chiche
authors.affiliation: Stem Cells & Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Roux
authors.affiliation: 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.
authors.forename: Mathieu
authors.initials: M
authors.lastname: von Joest
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: 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.
authors.forename: Sabela Búa
authors.initials: SB
authors.lastname: Aguín
authors.affiliation: 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.
authors.forename: Coralie
authors.initials: C
authors.lastname: Cazin
authors.affiliation: Cellular Plasticity & Disease Modelling, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
authors.forename: Rana
authors.initials: R
authors.lastname: Salam
authors.affiliation: Human Histopathology and Animal Models, Department of Infection & Epidemiology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.affiliation: 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.
authors.forename: Olinda
authors.initials: O
authors.lastname: Alegria
authors.affiliation: Human Histopathology and Animal Models, Department of Infection & Epidemiology, Institut Pasteur, 25 Rue du Dr Roux, Paris 75015, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Flamant
authors.affiliation: 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.
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.affiliation: 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.
authors.forename: Han
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D016922:Cellular Senescence; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism
keywords: IL-6; aging; cellular plasticity; cellular senescence; in vivo reprogramming; pluripotency; regeneration; skeletal muscle