Environmental signals constitute tissue activities that regulate stem cell activity. Epidermal injury is the key environmental signal. Bulge cells act quickly after injuries to the epidermis by producing short-lived cells that move to the center of the lesion. This process promotes healing.
Intrinsic signals include a protein-rich diet, which promotes the rate of division of stem cells in a process involving insulin signalling by inducing IGF-1. Other signalling pathways that regulate stem cell dormancy, multiplication and differentiation are Wnt, BMP and FGF18. The mesenchymal dermal papilla and the bulge (shown below) produce TGF-β, BMP, FGF and Wnt inhibitors, which work together to uphold dormancy during telogen (the resting stage). Initiation of Wnt signalling followed by the steadying and nuclear accumulation of β-catenin results in active growth (anagen). On the contrary, the associations between BMP ligands and receptors modulate the terminal differentiation pattern of hair shaft precursors. The differentiation of mature hair follicles is mediated by Notch signalling.
Stem cells of the hair follicle. Part a) shows the constituents of the niche environment while b) shows the response to injury.
Cell dynamics throughout the cell cycle.