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Myf6/MRF4 is a myogenic niche regulator required for the maintenance of the muscle stem cell pool
Author(s) -
Lazure Felicia,
Blackburn Darren M,
Corchado Aldo H,
Sahinyan Korin,
Karam Nabila,
Sharanek Ahmad,
Nguyen Duy,
Lepper Christoph,
Najafabadi Hamed S,
Perkins Theodore J,
JahaniAsl Arezu,
Soleimani Vahab D
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949499
Subject(s) - microbiology and biotechnology , biology , stem cell , myokine , skeletal muscle , myocyte , endocrinology
Abstract The function and maintenance of muscle stem cells (Mu SC s) are tightly regulated by signals originating from their niche environment. Skeletal myofibers are a principle component of the Mu SC niche 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, including EGF . EGFR signaling blocks p38 MAP kinase‐induced differentiation of muscle stem cells. Homozygous deletion of Myf6 causes a significant reduction in the ability of muscle to produce EGF , leading to a deregulation in EGFR signaling. 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 as EGF , in the muscle fiber which prevents muscle stem cell exhaustion by blocking their premature differentiation.