Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load
| Autor: | Lidan Zhang, Tamaki Kurosawa, Yasuyuki Ohkawa, Yasuyuki Saito, Akiyoshi Uezumi, Takashi Matozaki, Madoka Ikemoto-Uezumi, Kazutake Tsujikawa, So-ichiro Fukada, Thomas Braun, Takayuki Kaji, Akihiro Kaneshige, Ayasa Nakamura, Hayato Saito, Masatoshi Hori, Michael Potente, Shigeto Seno, Kazumitsu Maehara, Shuichi Watanabe |
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| Rok vydání: | 2022 |
| Předmět: |
YAP1
Mechanical load Stem Cells CD47 Mesenchymal stem cell Skeletal muscle CD47 Antigen Hypertrophy Cell Biology Biology Cell biology Muscle hypertrophy Myoblasts Mice medicine.anatomical_structure Downregulation and upregulation Cardiovascular and Metabolic Diseases Genetics medicine Animals Molecular Medicine Progenitor cell Stem cell Muscle Skeletal |
| Zdroj: | Cell Stem Cell |
| ISSN: | 1934-5909 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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