Damaged Myofiber-Derived Metabolic Enzymes Act as Activators of Muscle Satellite Cells

Autor: Hiroshi Masumoto, Yusuke Ono, Yoshifumi Tsuchiya, Yasuo Kitajima
Rok vydání: 2020
Předmět:
Zdroj: Stem Cell Reports
ISSN: 2213-6711
DOI: 10.1016/j.stemcr.2020.08.002
Popis: Summary Muscle satellite cells are normally quiescent but are rapidly activated following muscle damage. Here, we investigated whether damaged myofibers influence the activation of satellite cells. Our findings revealed that satellite cells are directly activated by damaged-myofiber-derived factors (DMDFs). DMDFs induced satellite cells to enter the cell cycle; however, the cells stayed at the G1 phase and did not undergo S phase, and these cells were reversible to the quiescent-like state. Proteome analysis identified metabolic enzymes, including GAPDH, as DMDFs, whose recombinant proteins stimulated the activation of satellite cells. Satellite cells pre-exposed to the DMDFs demonstrated accelerated proliferation ex vivo. Treatment with recombinant GAPDH prior to muscle injury promoted expansion of the satellite cell population in vivo. Thus, our results indicate that DMDFs are not only a set of biomarkers for muscle damage, but also act as moonlighting proteins involved in satellite cell activation at the initial step of muscle regeneration.
Graphical Abstract
Highlights • Damaged-myofiber-derived factors (DMDFs) activate satellite cells • DMDFs induce activation, but not proliferation, of satellite cells • Satellite cells activated by DMDFs are reversible to the quiescent-like state • DMDFs play an important role in the initial step of muscle regeneration
In this article, Tsuchiya et al. demonstrate that muscle satellite cells are directly activated by damaged-myofiber-derived factors (DMDFs). DMDFs promote population expansion of satellite cells during muscle regeneration. DMDFs are not only a set of biomarkers for muscle damage, but also act as functional proteins involved in satellite cell activation at the initial step of muscle regeneration.
Databáze: OpenAIRE