title: Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration.
abstract: Distinct cell populations with regenerative capacity have been reported to contribute to myofibres after skeletal muscle injury, including non-satellite cells as well as myogenic satellite cells. However, the relative contribution of these distinct cell types to skeletal muscle repair and homeostasis and the identity of adult muscle stem cells remain unknown. We generated a model for the conditional depletion of satellite cells by expressing a human diphtheria toxin receptor under control of the murine Pax7 locus. Intramuscular injection of diphtheria toxin during muscle homeostasis, or combined with muscle injury caused by myotoxins or exercise, led to a marked loss of muscle tissue and failure to regenerate skeletal muscle. Moreover, the muscle tissue became infiltrated by inflammatory cells and adipocytes. This localised loss of satellite cells was not compensated for endogenously by other cell types, but muscle regeneration was rescued after transplantation of adult Pax7(+) satellite cells alone. These findings indicate that other cell types with regenerative potential depend on the presence of the satellite cell population, and these observations have important implications for myopathic conditions and stem cell-based therapeutic approaches.
authors.affiliation: Institut Pasteur, Stem Cells and Development, CNRS URA 2578, 25 rue du Dr Roux, Paris, F-75015, France.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Sambasivan
authors.forename: Roseline
authors.initials: R
authors.lastname: Yao
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Laetitia
authors.initials: L
authors.lastname: Van Wittenberghe
authors.forename: Andràs
authors.initials: A
authors.lastname: Paldi
authors.forename: Barbara
authors.initials: B
authors.lastname: Gayraud-Morel
authors.forename: Hind
authors.initials: H
authors.lastname: Guenou
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
mesh_terms: D000818:Animals; D004167:Diphtheria Toxin / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism*
chemical_list: D004167:Diphtheria Toxin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse