Dermal sheath contraction powers stem cell niche relocation during hair cycle regression

Tissue homeostasis requires the balance of growth by cell production and regression through cellular loss. In the hair cycle during follicle regression, the niche traverses the skin through an unknown mechanism to reach the stem cells and prime regeneration. Here, by cell specific ablation and intravital imaging in live mice, we identify the follicle-lining dermal sheath as the key driver of tissue regression and niche relocation via smooth muscle contractile machinery that generates centripetal constriction force. We reveal the calcium/calmodulin/myosin light chain kinase pathway as the mechanism of sheath contraction that when blocked inhibits follicle contraction and impedes regression and niche relocation. Thus, our study identifies the dermal sheath as a smooth muscle that drives regression for reuniting niche and stem cells to regenerate tissue structure during homeostasis. Overall design: Dorsal skins were dissected from P5 mice dissociated into single cells, and FACS sorted for dermal sheath, dermal papilla, and dermal fibroblasts.