The Circadian Molecular Clock Creates Epidermal Stem Cell Heterogeneity

The study demonstrated that the circadian molecular clock created heterogeneity in murine epidermal stem cells, influencing their dormancy and activation cycles. Using genetically modified mouse models, researchers found that the core clock protein Bmal1 modulated stem cell regulatory genes, leading to varying activation predispositions. Disruption of this clock equilibrium, through deletion of Bmal1 or Per1/2, resulted in an imbalance in dormant stem cells, inefficient epidermal self-renewal, premature aging, and altered tumorigenesis. These findings highlighted the circadian clock's role in fine-tuning epidermal stem cell behavior, impacting homeostasis, aging, and cancer predisposition.