The central clock drives metabolic rhythms in muscle stem cells

Abstract

Satellite cells (SCs), the skeletal muscle resident stem cells, maintain a state of quiescence yet exhibit robust circadian oscillations at the transcriptional level. How SC circadian rhythms are controlled is not well understood. Here, we use SC-specific reconstitution of the essential clock gene Bmal1 in mice to elucidate the role of the local SC clock and its interplay with the central clock in the brain. We find that 24-h rhythmicity of metabolic genes in SCs depends on central clock inputs, independent of the SC clock, and identify rhythmic feeding-fasting cycles as the key brain clock-dependent output controlling their oscillation. Functionally, central signals regulate SC metabolic state and SC-mediated muscle repair, and we identify intact autophagic function as a prerequisite for correct oscillation of metabolic transcripts. Overall, we show that the central clock acts dominantly via feeding-fasting cycles to control rhythmic gene expression and metabolic state in quiescent SCs.