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Nat Commun. 2017 Sep 22;8(1):669. doi: 10.1038/s41467-017-00522-7.

Macrophage-released ADAMTS1 promotes muscle stem cell activation.

Author information

1
Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.
2
Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
3
Program in Cancer Biology, Stanford University, Stanford, CA, 94305, USA.
4
Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, CA, 94305, USA.
5
Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA. feldman@stanford.edu.
6
Program in Cancer Biology, Stanford University, Stanford, CA, 94305, USA. feldman@stanford.edu.
7
Stanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA. feldman@stanford.edu.
8
Program in Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA. feldman@stanford.edu.

Abstract

Coordinated activation of muscle stem cells (known as satellite cells) is critical for postnatal muscle growth and regeneration. The muscle stem cell niche is central for regulating the activation state of satellite cells, but the specific extracellular signals that coordinate this regulation are poorly understood. Here we show that macrophages at sites of muscle injury induce activation of satellite cells via expression of Adamts1. Overexpression of Adamts1 in macrophages in vivo is sufficient to increase satellite cell activation and improve muscle regeneration in young mice. We demonstrate that NOTCH1 is a target of ADAMTS1 metalloproteinase activity, which reduces Notch signaling, leading to increased satellite cell activation. These results identify Adamts1 as a potent extracellular regulator of satellite cell activation and have significant implications for understanding the regulation of satellite cell activity and regeneration after muscle injury.Satellite cells are crucial for growth and regeneration of skeletal muscle. Here the authors show that in response to muscle injury, macrophages secrete Adamts1, which induces satellite cell activation by modulating Notch1 signaling.

PMID:
28939843
PMCID:
PMC5610267
DOI:
10.1038/s41467-017-00522-7
[Indexed for MEDLINE]
Free PMC Article

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