miR-378-mediated glycolytic metabolism enriches the Pax7Hi subpopulation of satellite cells

• Published in: Cell regeneration Vol. 11; no. 1; pp. 1 - 11
• Main Authors: Li, Hu, Kang, Lin, Wu, Rimao, Li, Changyin, Zhang, Qianying, Zhong, Ran, Jia, Lijing, Zhu, Dahai, Zhang, Yong
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 02.04.2022; Springer Nature B.V; SpringerOpen
• Subjects: AKT1 protein; Basal lamina; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell self-renewal; Dehydrogenases; FOXO1 protein; Gene expression; Glycolysis; glycolytic metabolism; Homeostasis; Life Sciences; Metabolism; miRNA; miRNAs; muscle regeneration; Musculoskeletal system; Physiology; Regenerative medicine; Research Article; Rodents; Roles; Sarcolemma; Satellite cells; Skeletal muscle; Skeletal Muscle Regeneration; Stem cell transplantation; Stem Cells; Transgenic mice; muscle regeneration; glycolytic metabolism; miRNAs; satellite cells
• ISSN: 2045-9769; 2045-9769
• DOI: 10.1186/s13619-022-00112-z

Adult skeletal muscle stem cells, also known satellite cells (SCs), are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma. Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration. Herein, we demonstrate that microRNA 378 (miR-378) regulates glycolytic metabolism in skeletal muscle fibers, as evidenced by analysis of myofiber-specific miR-378 transgenic mice (TG). Subsequently, we evaluate SC function and muscle regeneration using miR-378 TG mice. We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs. Furthermore, we show that the miR-378-mediated metabolic switch enriches Pax7 Hi SCs, accounting for impaired muscle regeneration in miR-378 TG mice. Mechanistically, our data suggest that miR-378 targets the Akt1/FoxO1 pathway, which contributes the enrichment of Pax7 Hi SCs in miR-378 TG mice. Together, our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.