Lactate production drives hair follicle stem cell activation

Hair follicle stem cells are quiescent, long-lived cells that are responsible for maintaining the cellular homeostasis of the follicle. While normally dormant, HFSCs quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms, and is thought to act as a tumor suppressive mechanism. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we took advantage of these findings to identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a unique metabolic state that endows them with the ability to remain dormant and yet quickly respond to appropriate proliferative stimuli.