期刊
DEVELOPMENT
卷 138, 期 17, 页码 3647-3656出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.067587
关键词
Skeletal muscle stem cell; Diphtheria toxin; Regeneration; Mouse
资金
- Association Francaise contre les Myopathies (AFM)
- Institut Pasteur
- Institut Pasteur, AFM
- Agence Nationale de la Recherche [ANR-06-BLAN-0039]
- Eurosystem and Optistem FP7 programmes
- French Fondation pour la Recherche Medicale
- Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0039] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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