LB1012 Dermal sheath mechanosignaling activation of TGF-β controls progenitor death during hair follicle regression

Abstract

Epithelial-mesenchymal crosstalk is vital for balancing expansion and regression of the progenitor cell pool during tissue turnover. In the hair growth cycle, little is known about the mechanisms underlying the regulated cell death during follicle regression that precedes each regeneration and hair re-growth. Here, we discover that the dermal sheath smooth muscle, which lines all follicles, controls progenitor death via transforming growth factor (TGF)-β mechanosignaling. The sheath secretes TGF-β, which is first stored as an inactive, latent complex in the basement membrane extracellular matrix. The sheath then contracts to free TGF-β for essential signaling to progenitors for cell death regulation and regression. Finally, we identify Integrin-alpha-V on the sheath surface as the molecular link for force-mediated TGF-β release. Our study establishes the dermal sheath as a mechanosignaling niche that controls progenitor pool reduction through mechanical force, signal activation and cell-cell communication.