Melatonin-Mediated Circadian Rhythm Signaling Exhibits Bidirectional Regulatory Effects on the State of Hair Follicle Stem Cells

The development and regulation of hair are widely influenced by biological rhythm signals. Melatonin plays a crucial role as a messenger in transmitting biological rhythm signals, and its impact on hair development has been well documented. During the process of hair follicle reconstruction, hair follicle stem cells (HFSCs) are the most important cell type, but the regulatory effect of melatonin on the state of HFSCs is still not fully understood. Therefore, it is necessary to conduct a more comprehensive characterization of the effects of melatonin on the state of hair follicle stem cells. The research results indicate that HFSCs express retinoic acid receptor-related orphan receptor alpha (<i>Rorα</i>), and melatonin inhibits the expression level of RORA. Experimental results from CUT&Tag, CUT&RUN, and dual luciferase reporter assays demonstrate that <i>Foxc1</i> is a downstream target gene of RORA, with RORA regulating <i>Foxc1</i> expression by binding to the promoter region of <i>Foxc1</i>. The CCK-8 assay results show that low doses of melatonin upregulate the survival rate of hair follicle stem cells, while high doses have the opposite effect. The knockdown of <i>Foxc1</i> reverses the inhibitory effect of high-dose melatonin on the survival rate of hair follicle stem cells. Based on these findings, we believe that melatonin-mediated circadian signals exert a bidirectional regulatory effect on the state of HFSCs.