MuSK-BMP signaling in adult muscle stem cells maintains quiescence and regulates myofiber size.
Autor: | Madigan LA, Jaime D, Chen I, Fallon JR |
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Jazyk: | angličtina |
Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 18. Date of Electronic Publication: 2024 Jul 18. |
DOI: | 10.1101/2023.05.17.541238 |
Abstrakt: | A central question in adult stem cell biology is elucidating the signaling pathways regulating their dynamics and function in diverse physiological and age-related contexts. Muscle stem cells in adults (Satellite Cells; SCs) are generally quiescent but can activate and contribute to muscle repair and growth. Here we tested the role of the MuSK-BMP pathway in regulating adult SC quiescence by deletion of the BMP-binding MuSK Ig3 domain ('ΔIg3-MuSK'). At 3 months of age SC and myonuclei numbers and myofiber size were comparable to WT. However, at 5 months of age SC density was decreased while myofiber size, myonuclear number and grip strength were increased - indicating that SCs had activated and productively fused into the myofibers over this interval. Transcriptomic analysis showed that SCs from uninjured ΔIg3-MuSK mice exhibit signatures of activation. Regeneration experiments showed that ΔIg3-MuSK SCs maintain full stem cell function. Expression of ΔIg3-MuSK in adult SCs was sufficient to break quiescence and increase myofiber size. We conclude that the MuSK-BMP pathway regulates SC quiescence and myofiber size in a cell autonomous, age-dependent manner. Targeting MuSK-BMP signaling in muscle stem cells thus emerges a therapeutic strategy for promoting muscle growth and function in the settings of injury, disease, and aging. Highlights: MuSK, in its role as a BMP co-receptor, regulates adult muscle stem cell quiescenceThe MuSK-BMP pathway acts cell autonomouslyIncreased muscle size and function with preservation of myonuclear density and stemness in mice with attenuated MuSK-BMP signaling. |
Databáze: | MEDLINE |
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