Hair Follicle Epidermal Stem Cells Define a Niche for Tactile Sensation

The heterogeneity and compartmentalization of stem cells is a common principle in many epithelia, and is known to function in epithelial maintenance, but its other physiological roles remain elusive. Here we show transcriptional and anatomical contributions of compartmentalized epidermal stem cells (EpSCs) in tactile sensory unit formation in the hair follicle (HF). EpSCs in the follicle upper-bulge, where mechanosensory lanceolate complexes (LCs) innervate, express a unique set of extracellular matrix (ECM) and neurogenesis-related genes. These EpSCs deposit an ECM protein EGFL6 into the collar matrix, a novel ECM that tightly ensheathes LCs. EGFL6 is required for the proper patterning, touch responses, and αv integrin-enrichment of LCs. By maintaining a quiescent original EpSC niche, the old bulge, EpSCs provide anatomically stable HF-LC interfaces, irrespective of the stage of follicle regeneration cycle. Thus, compartmentalized EpSCs provide a niche linking the HF and the nervous system throughout the hair cycle.