In mammals, epidermal stem cells located in the bulge region of the hair follicle undergo cycles of activation and dormancy to ensure hair renewal. However, not all these stem cells respond to activation at the same time, and the reason behind this heterogeneity has been unclear.

Aznar-Benitah and colleagues (10.1038/nature10649) now show that the circadian rhythm machinery modulates gene expression in the bulge to prime a subpopulation of cells for activation. They observed that a circadian reporter is heterogeneously expressed in the bulge stem cells. Cells with high circadian activity expressed higher levels of genes involved in stem cell proliferation and hair growth, whereas cells with low activity exhibited a dormant expression profile. The authors showed that Bmal1, a master regulator of clock activity, directly modulates the rhythmic expression of genes linked to activation. Its deletion reduced stem cell proliferation in the bulge, whereas loss of a negative clock regulator had the reverse effect. Bmal1 knockout animals displayed signs of premature ageing with defects in hair renewal, but were less prone to Ras-mediated skin tumorigenesis. Remarkably, epidermal stem cells of the interfollicular epidermis, which are constantly cycling, were unaffected by Bmal1 loss. It will be interesting to see if other adult stem cells with cyclic activity are also under circadian control.