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Macrophage-released ADAMTS1 promotes muscle stem cell activation

Author

Listed:
  • Hongqing Du

    (Stanford University)

  • Chung-Hsuan Shih

    (Stanford University)

  • Michael N. Wosczyna

    (Stanford University)

  • Alisa A. Mueller

    (Stanford University
    Stanford University)

  • Joonseok Cho

    (Stanford University)

  • Abhishek Aggarwal

    (Stanford University)

  • Thomas A. Rando

    (Stanford University
    Stanford University
    Stanford University)

  • Brian J. Feldman

    (Stanford University
    Stanford University
    Stanford University
    Stanford University)

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.

Suggested Citation

  • Hongqing Du & Chung-Hsuan Shih & Michael N. Wosczyna & Alisa A. Mueller & Joonseok Cho & Abhishek Aggarwal & Thomas A. Rando & Brian J. Feldman, 2017. "Macrophage-released ADAMTS1 promotes muscle stem cell activation," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00522-7
    DOI: 10.1038/s41467-017-00522-7
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    Cited by:

    1. David E. Lee & Lauren K. McKay & Akshay Bareja & Yongwu Li & Alastair Khodabukus & Nenad Bursac & Gregory A. Taylor & Gurpreet S. Baht & James P. White, 2022. "Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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