Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration

The study explored the importance of Wnt signaling in the regeneration of pigmented hair, focusing on the interaction between epithelial stem cells (EpSCs) and melanocyte stem cells (McSCs). It was found that Wnt signaling is essential for the coordinated activation and differentiation of these stem cells within the hair follicle. Activation of Wnt signaling in McSCs leads to their differentiation into pigment-producing melanocytes, while in EpSCs, it triggers hair follicle formation and controls McSC proliferation. The study used genetic mouse models to demonstrate that Wnt signaling serves as both an intrinsic and extrinsic regulator for these stem cells. The research also showed that constitutive stabilization of β-catenin in McSCs causes premature differentiation and loss of these cells, leading to premature hair graying, while loss of β-catenin inhibits melanocyte proliferation and differentiation, also resulting in gray hair. The study involved more than 15 mice from five litters for gray hair coat observation, 10 mice from more than four separate litters for pigmentation analysis, and over 60 longitudinal hair follicle sections from at least three different mice for immunohistochemical and histological analysis. The findings suggest that targeting Wnt signaling could be a potential strategy for treating pigmentation disorders and that the coordinated action between EpSCs and McSCs is crucial for pigmented hair regeneration.