Transcriptomic profiling of mouse fibro/adipogenic progenitors (FAPs) upon melatonin treatment in vitro

The purpose of this study is to investigate how melatonin-influenced promyogenic factor secreted from fibro-adipogenic progenitors (FAPs) regulate muscle regeneration and muscle cell fusion during muscle repair. We highlighted the role of melatonin in regulating crosstalk between muscle stem cells and FAPs during muscle regeneration. Mice that were treated with melatonin exhibited improved muscle regeneration and reduced intramuscular fat deposition, which were associated with enhanced myogenesis, remodeled lipid metabolism and reduced immune cell infiltration. Notably, melatonin did not exert positive effects on cell fusion and myotube formation during differentiation. Interestingly, melatonin repressed fibro-adipogenic progenitor (FAP) adipogenesis in a dose-dependent manner in vitro. Furthermore, melatonin treatment enhanced the pro-myogenic effects of FAPs, which stimulated GDF10 secretion to promote muscle cell fusion and induce myotube hypertrophy. Overall design: Transcriptomic profiling was performed on RNA from isolated FAPs treated by melatonin or vehicle for 24 hours in vitro. Fibro-adipogenic progenitors (FAPs) were isolated from uninjured tibialis anterior, gastrocnemius and quadriceps of wildtype C57BL/6J male mice. After 48 h, FAPs were treated with vehicle or melatonin for 24 h in vitro. 4 biological replicates were used for each condition.