Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation.

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Published in Cell Stem Cell, v. 20, issue 1, p. 56-69.

© 2016 Elsevier Inc.

This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Research was supported by NIH grant AR065337 and the Jeane B. Kempner Postdoctoral Scholar Award to C.S.F.; NIH grants AG34453 to C.A.P. and AR060701 and AG049806 to C.A.P. and J.J.M.; and the NIH National Center for Advancing Translational Sciences, through Grant UL1TR000117.

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Commentary on this article is available from the following piece:

Spinazzola, J. M., & Gussoni, E. (2017). Exosomal small talk carries strong messages from muscle stem cells. Cell Stem Cell. 20: 1–3, 5. https://doi.org/10.1016/j.stem.2016.12.009

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