Abstract

The ability to sense and to respond to the external environment capacitates tissue stem cells to tailor their activity to meet organismal needs. It has long been observed in human that external irritation leads to acquired hypertrichosis, but the mechanism remains unclear. We found that, in mice, hair follicle stem cells (HFSCs) are activated by external irritation with prominent hair regeneration. The external irritation is not directly sensed by HFSCs themselves but by niche adipocytes which undergo lipolysis to activate HFSCs. Taken up by HFSCs, fatty acids released by adipocytes activate HFSCs by priming HFSCs for fatty acid oxidation and increasing mitochondrial oxidative phosphorylation capacity for ATP production. Inhibiting lipolysis, fatty acid uptake or fatty acid oxidation suppresses irritation-induced hair regeneration. Therefore, adipocytes form an injury-sensing niche that enables HFSCs to respond to external irritation to begin a new round of hair growth for skin protection.

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