Lactate dehydrogenase activity drives hair follicle stem cell activation

Hair follicle stem cells (HFSCs) are typically dormant but quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is regulated by various intrinsic and extrinsic mechanisms. In this study, we provide multiple lines of evidence showing that HFSCs rely on glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Importantly, lactate production appears to be essential for the activation of HFSCs, as the deletion of lactate dehydrogenase (Ldha) prevented their activation. On the other hand, genetically enhancing lactate production in HFSCs by deleting mitochondrial pyruvate carrier 1 (Mpc1) accelerated their activation and hair cycle progression. Lastly, we identify small molecules that stimulate lactate production by increasing Myc levels or inhibiting Mpc1 carrier activity, which can topically induce the hair cycle. These findings suggest that HFSCs maintain a metabolic state that allows them to UK 5099 remain dormant but rapidly respond to proliferative signals when needed.