The central clock drives metabolic rhythms in muscle stem cells

Abstract

Circadian rhythms are essential for organismal health. Satellite cells (SCs), the muscle resident stem cells, maintain a state of quiescence yet exhibit robust circadian oscillations at the transcriptional level. Although peripheral clocks have been extensively studied in various tissues, how the intrinsic clock of stem cells interacts with the central, distal clock is largely unknown. We used SC-specific reconstitution of the essential clock gene Bmal1 to elucidate the role of the local SC clock and its interplay with the central clock in the mouse brain and found that daily transcriptional control of metabolic processes in SCs depend on central clock input, independent of the SC clock. Central clock-driven genes were involved in lipid metabolism, functionally important for SC-mediated muscle repair, and autophagy was required for their oscillation. In summary, we provide the first evidence of circadian coordination of central and local clocks for control of rhythmic gene expression in quiescent stem cells. HighlightsO_LIBrain:satellite cell clock communication restores rhythms of core clock machinery in quiescent satellite cells C_LIO_LIBrain inputs are the dominant regulator of transcript rhythms in SCs, driving the oscillation of lipid metabolic genes. C_LIO_LIAutophagy in satellite cells is required for the oscillation of lipid metabolic genes. C_LIO_LIEarly phases of muscle regeneration depend on brain-driven circadian signals. C_LI