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.

Details

Title
Macrophage-released ADAMTS1 promotes muscle stem cell activation
Author
Du, Hongqing 1 ; Chung-Hsuan Shih 1 ; Wosczyna, Michael N 2 ; Mueller, Alisa A 3 ; Cho, Joonseok 1 ; Aggarwal, Abhishek 1 ; Rando, Thomas A 4 ; Feldman, Brian J 5 

 Department of Pediatrics, Stanford University, Stanford, CA, USA 
 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA 
 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Program in Cancer Biology, Stanford University, Stanford, CA, USA 
 Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Program in Cancer Biology, Stanford University, Stanford, CA, USA; Paul F. Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, CA, USA 
 Department of Pediatrics, Stanford University, Stanford, CA, USA; Program in Cancer Biology, Stanford University, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Program in Regenerative Medicine, Stanford University, Stanford, CA, USA 
Pages
1-11
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1953961337
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.