A review of the circadian regulation of stem cells: harnessing the internal body clock for enhanced regenerative therapies

• Core clock components (CLOCK, BMAL1) directly regulate stem-cell signaling pathways (Wnt, Notch, Hedgehog) via transcriptional control and chromatin remodeling. • Stem-cell pathways feedback to modulate circadian clock amplitude and phase, creating a bidirectional regulatory loop essential for tissue homeostasis. • Disruption of circadian-stem cell crosstalk leads to stem-cell exhaustion, impaired regeneration, and accelerated ageing, and may promote tumorigenesis. • Chronotherapeutic strategies that time stem-cell-based interventions to intrinsic circadian phases could enhance therapeutic efficacy and safety.