Dermal adipocytes activate hair follicle stem cells through metabolic communication [SDS II]

The ability of tissue stem cells to sense and respond to their surroundings enables them to adapt their activity to meet the needs of the organism. External irritation has long been observed in humans to cause acquired hypertrichosis, but the mechanism is unknown. We discovered that external irritation activates hair follicle stem cells (HFSCs), leading to substantial hair regeneration in mice. The external irritation is sensed by niche adipocytes, which undergo lipolysis to activate HFSCs, rather than by the HFSCs themselves. Fatty acids released by adipocytes are taken up by HFSCs and activate them by priming them for fatty acid oxidation and increasing the mitochondrial oxidative phosphorylation capacity for ATP production. Inhibiting lipolysis, fatty acid uptake, or fatty acid oxidation restricts irritation-induced hair regeneration. As a result, adipocytes create an injury-sensing niche, allowing HFSCs to respond to external irritation by initiating a new round of hair growth to protect the skin.