Title : Extracellular vesicles from activated dermal fibroblasts stimulate hair follicle growth through dermal papilla-secreted norrin
Dermal papilla cells play a pivotal role in the regulation of hair follicle growth, formation, and cycling, mainly through paracrine mechanisms. In the last decade, extracellular vesicles (EVs) have been recognized as a new paracrine mechanism that can modify the physiological state of recipient cells by transferring biological material. Herein, we investigated the effect of EVs isolated from stimulated human dermal fibroblasts on dermal papilla cell activation and hair follicle growth. We found that these EVs (st-EVs) enhanced hair follicle growth ex vivo. Comparative transcriptomic analysis on dermal papilla cells identified specific activation of the NDP gene, encoding the non-Wnt ligand norrin. We found that norrin was secreted by st-EVs-stimulated dermal papilla cell activating in a non-cell autonomous manner ?-catenin pathway in follicular keratinocytes and hair growth ex vivo. While norrin-specific receptor Frizzled4 was barely detected in human follicular keratinocytes, we found its presence on dermal fibroblasts EVs. Accordingly, dermal fibroblasts EVs provided Frizzled4 to potentiate norrin effects ex-vivo. Our study identifies dermal fibroblasts EVs as efficient activators of dermal papilla cells and norrin as a novel modulatory player in hair follicle physiopathology. Le Riche et al. Stem cells 2019.
Audience Take Away:
discover Norrin, as a new actor of hair follicle physiopathology
discover that extracellular microvesicles could communicate hair growth signalling
discover that extracellular microvesicles can provide receptors to recipeint cells for signalling