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  Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load

Kaneshige, A., Kaji, T., Zhang, L., Saito, H., Nakamura, A., Kurosawa, T., et al. (2022). Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load. CELL STEM CELL, 29(2), 265-280. doi:10.1016/j.stem.2021.11.003.

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 Creators:
Kaneshige, Akihiro, Author
Kaji, Takayuki, Author
Zhang, Lidan, Author
Saito, Hayato, Author
Nakamura, Ayasa, Author
Kurosawa, Tamaki, Author
Ikemoto-Uezumi, Madoka, Author
Tsujikawa, Kazutake, Author
Seno, Shigeto, Author
Hori, Masatoshi, Author
Saito, Yasuyuki, Author
Matozaki, Takashi, Author
Maehara, Kazumitsu, Author
Ohkawa, Yasuyuki, Author
Potente, Michael1, Author              
Watanabe, Shuichi2, Author              
Braun, Thomas2, Author              
Uezumi, Akiyoshi, Author
Fukada, So-ichiro, Author
Affiliations:
1Angiogenesis & Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591701              
2Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              

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 Abstract: Adaptation to mechanical load, leading to enhanced force and power output, is a characteristic feature of skeletal muscle. Formation of new myonuclei required for efficient muscle hypertrophy relies on prior activation and proliferation of muscle stem cells (MuSCs). However, the mechanisms controlling MuSC expansion under conditions of increased load are not fully understood. Here we demonstrate that interstitial mesenchymal progenitors respond to mechanical load and stimulate MuSC proliferation in a surgical mouse model of increased muscle load. Mechanistically, transcriptional activation of Yes-associated protein 1 (Yap1)/transcriptional coactivator with PDZ-binding motif (Taz) in mesenchymal progenitors results in local production of thrombospondin-1 (Thbs1), which, in turn, drives MuSC proliferation through CD47 signaling. Under homeostatic conditions, however, CD47 signaling is insufficient to promote MuSC proliferation and instead depends on prior downregulation of the Calcitonin receptor. Our results suggest that relayed signaling between mesenchymal progenitors and MuSCs through a Yap1/Taz-Thbs1-CD47 pathway is critical to establish the supply of MuSCs during muscle hypertrophy.

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 Dates: 2021-12-012022-02-03
 Publication Status: Published in print
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 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000753471000011
DOI: 10.1016/j.stem.2021.11.003
PMID: 34856120
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Title: CELL STEM CELL
Source Genre: Journal
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Pages: - Volume / Issue: 29 (2) Sequence Number: - Start / End Page: 265 - 280 Identifier: ISSN: 1934-5909