Journal
EMBO REPORTS
Volume 21, Issue 12, Pages -Publisher
WILEY
DOI: 10.15252/embr.201949499
Keywords
muscle stem cells; Myf6; myogenic factors; myokines; skeletal muscles
Categories
Funding
- Canadian Institute of Health Research (CIHR) [PJT-156087]
- NSERC [RGPIN-2015-06774]
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The function and maintenance of muscle stem cells (MuSCs) are tightly regulated by signals originating from their niche environment. Skeletal myofibers are a principle component of the MuSCniche and are in direct contact with the muscle stem cells. Here, we show that Myf6 establishes a ligand/receptor interaction between muscle stem cells and their associated muscle fibers. Our data show that Myf6 transcriptionally regulates a broad spectrum of myokines and muscle-secreted proteins in skeletal myofibers, includingEGF.EGFRsignaling blocks p38MAPkinase-induced differentiation of muscle stem cells. Homozygous deletion of Myf6 causes a significant reduction in the ability of muscle to produceEGF, leading to a deregulation inEGFRsignaling. Consequently, although Myf6-knockout mice are born with a normal muscle stem cell compartment, they undergo a progressive reduction in their stem cell pool during postnatal life due to spontaneous exit from quiescence. Taken together, our data uncover a novel role for Myf6 in promoting the expression of key myokines, such asEGF, in the muscle fiber which prevents muscle stem cell exhaustion by blocking their premature differentiation.
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