Molecular clocks, satellite cells, and skeletal muscle regeneration

Skeletal muscle comprises approximately 50% of individual body mass and plays vital roles in locomotion, heat production, and whole body metabolic homeostasis. This tissue exhibits a robust diurnal rhythm that is under control of the suprachiasmatic nu-cleus (SCN) region of the hypothalamus. The SCN acts as a central coordinator of circadian rhythms, while cell-autonomous peripheral clocks are located within almost all other tissues/organs in the body. Synchronization of the peripheral clocks in muscles (and other tissues) together with the central clock is crucial to ensure temporally coordinated physiology across all organ systems. By virtue of its mass, human skeletal muscle contains the largest collection of peripheral clocks, but within mus-cle resides a local stem cell population, satellite cells (SCs), which have their own functional molecular clock, independent of the numerous muscle clocks. Skeletal muscle has a daily turnover rate of 1%-2%, so the regenerative capacity of this tissue is impor-tant for whole body homeostasis/repair and depends on successful SC myogenic progression (i.e., proliferation, differentiation, and fusion). Emerging evidence suggests that SC-mediated muscle regeneration may, in part, be regulated by molecular clocks involved in SC-specific diurnal transcription. Here we provide insights on molecular clock regulation of muscle regeneration/ repair and provide a novel perspective on the interplay between SC-specific molecular clocks, myogenic programs, and cell cycle kinetics that underpin myogenic progression.

Automated summary

Skeletal muscle, which accounts for approximately 50% of body mass, displays a robust diurnal rhythm under the control of the suprachiasmatic nucleus (SCN) in the hypothalamus. Synchronization of peripheral clocks in muscles with the central clock is crucial for coordinated physiological functions. Satellite cells (SCs), a local stem cell population within muscles, have their own functional molecular clock that may regulate SC-mediated muscle regeneration. Understanding the interplay between SC-specific molecular clocks, myogenic programs, and cell cycle kinetics is important for muscle regeneration and repair.