Nerve-Derived Sonic Hedgehog Defines a Niche for Hair Follicle Stem Cells Capable of Becoming Epidermal Stem Cells

The study concluded that nerve-derived Sonic Hedgehog (Shh) signaling was crucial for maintaining a niche for Gli1(+) hair follicle stem cells (HFSCs) in the upper bulge, enabling them to become epidermal stem cells during wound healing. These HFSCs were multipotent, capable of regenerating the anagen follicle, and self-renewing over multiple hair cycles. Denervation experiments in mice confirmed that Shh signaling from sensory neurons was essential for maintaining the molecular identity of these cells, although not necessary for their survival. The findings underscored the importance of the perineural microenvironment in stem cell plasticity and suggested potential therapeutic applications for skin repair and regeneration.