Myogenic Precursor Cells Show Faster Activation and Enhanced Differentiation in a Male Mouse Model Selected for Advanced Endurance Exercise Performance

Abstract

Satellite cells (SATC), the most abundant skeletal muscle stem cells, play a main role in muscle plasticity, including the adaptive response following physical activity. Thus, we investigated how long-term phenotype selection of male mice for high running performance (Dummerstorf high Treadmill Performance; DUhTP) affects abundance, creatine kinase activity, myogenic marker expression (Pax7, MyoD), and functionality (growth kinetics, differentiation) of SATC and their progeny. SATC were isolated from sedentary male DUhTP and control (Dummerstorf Control; DUC) mice at days 12, 43, and 73 of life and after voluntary wheel running for three weeks (day 73). Marked line differences occur at days 43 and 73 (after activity). At both ages, analysis of SATC growth via xCELLigence system revealed faster activation accompanied by a higher proliferation rate and lower proportion of Pax7+ cells in DUhTP mice, indicating reduced reserve cell formation and faster transition into differentiation. Cultures from sedentary DUhTP mice contain an elevated proportion of actively proliferating Pax7+/MyoD+ cells and have a higher fusion index leading to the formation of more large and very large myotubes at day 43. This robust hypertrophic response occurs without any functional load in the donor mice. Thus, our selection model seems to recruit myogenic precursor cells/SATC with a lower activation threshold that respond more rapidly to external stimuli and are more primed for differentiation at the expense of more primitive cells.