The central clock drives metabolic rhythms in muscle stem cells

Oct 2, 2025Cell reports

The body’s main internal clock controls daily energy patterns in muscle stem cells

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

The 24-hour rhythm of metabolic genes in satellite cells is influenced by central clock inputs.

Satellite cells, which are stem cells in skeletal muscle, display circadian oscillations in gene expression.
The local satellite cell clock is not required for the rhythmicity of metabolic genes.
Feeding-fasting cycles are identified as the primary output from the central clock that affects satellite cell function.
Central signals are linked to the metabolic state of satellite cells and their ability to repair muscle.
Intact autophagic function is necessary for the proper oscillation of metabolic transcripts in satellite cells.

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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.