Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development

Abstract

Satellite cells are resident myogenic progenitors in postnatal skeletal muscle involved in muscle postnatal growth and adult regenerative capacity. Here, we identify and describe a population of muscle-resident stem cells, which are located in the interstitium, that express the cell stress mediator PW1 but do not express other markers of muscle stem cells such as Pax7. PW1+/Pax7 interstitial cells (PICs) are myogenic in vitro and efficiently contribute to skeletal muscle regeneration in vivo as well as generating satellite cells and PICs. Whereas Pax7 mutant satellite cells show robust myogenic potential, Pax7 mutant PICs are unable to participate in myogenesis and accumulate during postnatal growth. Furthermore, we found that PICs are not derived from a satellite cell lineage. Taken together, our findings uncover a new and anatomically identifiable population of muscle progenitors and define a key role for Pax7 in a non-satellite cell population during postnatal muscle growth.

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Figure 1: PW1 identifies two distinct populations in postnatal muscle under the regulation of Pax7.
Figure 2: PICs are enriched in the muscle-resident Sca1+/CD34+ population.
Figure 3: PICs spontaneously convert to skeletal myogenic cells via a Pax7-dependent pathway.
Figure 4: Pax7 is required for PICs to participate in myogenesis.
Figure 5: PICs are bipotent and give rise to smooth and skeletal muscle.
Figure 6: PICs are myogenic and recolonize the PIC niche in vivo.
Figure 7: PICs are not derived from satellite cells.

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Acknowledgements

We gratefully thank F. Relaix for fruitful discussions and critical reading of the manuscript. We thank A. Galy, E. Negroni and L. Arandel for technical advice and C. Blanc (Cytométrie en Flux platform, Institut Fédératif de Recherche 113) for FACs assistance. This work was supported by a grant from the NIH (NCI PO1 CA80058-06, subproject 3), a French Ministry of Research 'Chaire d'Excellence' to D.S. and the Muscular Dystrophy Association of America to D.S. and E.R.G. K.M. is a recipient of an INSERM 'contrat de jeunes chercheurs'. B.C. is a recipient of a grant from Fondation pour la Recherche Médicale (FRM). E.R.G. is supported in part by the Inserm Avenir Program. This work benefited from funding from the European Community's Seventh Framework Programme project OPTISTEM (Optimization of stem cell therapy for degenerative epithelial and muscle diseases contract number Health-F5-2009-223098). The Myology Group is the beneficiary of a Strategic Plan Support from the Association Française contre les Myopathies (AFM) and is affiliated with the Institute of Myology/ Association Institut Myologie.

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All authors designed research; K.J.M., A.P., B.C., A.P. and V.B. performed research; B.C., V.B. and E.R.G. contributed new reagents/analytic tools; all authors analysed data and K.J.M., G.M. and D.A.S. wrote the paper.

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Correspondence to David A. Sassoon.

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Mitchell, K., Pannérec, A., Cadot, B. et al. Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nat Cell Biol 12, 257–266 (2010). https://doi.org/10.1038/ncb2025

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