1407 Mechanical force activation of TGF-β signaling controls hair follicle regression

The precise mechanisms that regulate the cell death during the physiological hair follicle regression of each hair growth cycle are largely unknown. Here, we uncover that the dermal sheath smooth muscle, which lines all follicles, controls progenitor apoptosis via mechanosignaling of the transforming growth factor (TGF)-β pathway. During hair growth, the dermal sheath first secretes TGF-β as an inactive, latent complex, which gets stored in the basement membrane extracellular matrix. During hair follicle regression, the sheath then contracts to mechanically free TGF-β, which then signals to progenitors to regulate cell death. Mechanistically, we identify Integrin-alpha-V on the sheath cell surface as the molecular link that directly connects sheath cell forces with extracellular matrix TGF-β release. Overall, this establishes the dermal sheath as a mechanosignaling niche that controls progenitor pool reduction through mechanical force, signal activation and cell-cell communication.