Extracellular Vesicles from Activated Dermal Fibroblasts Stimulate Hair Follicle Growth Through Dermal Papilla‐Secreted Norrin. (25th June 2019)

• Record Type: Journal Article
• Authors: le Riche, Alizée; Aberdam, Edith; Marchand, Laëtitia; Frank, Elie; Jahoda, Colin; Petit, Isabelle; Bordes, Sylvie; Closs, Brigitte; Aberdam, Daniel
• Is Part Of: Stem cells. Volume 37:Number 9(2019)
• Page Start: 1166
• Page End: 1175
• Publication Date: 2019-06-25
• Subjects: Norrin -- NDP -- Extracellular vesicles -- Exosomes -- Dermal papilla -- β‐Catenin -- Hair follicle -- Follicular keratinocytes -- Fzd4; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3043
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Dermal papilla cells (DPCs) play a pivotal role in the regulation of hair follicle (HF) 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 (DFs) on DPC activation and HF growth. We found that these EVs (st‐EVs) enhanced HF growth ex vivo. Comparative transcriptomic analysis on DPCs identified specific activation of the NDP gene, encoding the non‐Wnt ligand Norrin. We found that Norrin was secreted by st‐EVs‐stimulated DPCs activating in a noncell autonomous manner β‐catenin pathway in follicular keratinocytes (human HF keratinocyte [HHFK]) and hair growth ex vivo. Although Norrin‐specific receptor Frizzled4 was barely detected in HHFK, we found its presence in DF‐EVs. Accordingly, DF‐EVs provided Frizzled4 to potentiate Norrin effects ex vivo. Our study identifies DF‐EVs as efficient activators of DPCs and Norrin as a novel modulatory player in HF physiopathology.Stem Cells 2019;37:1166–1175 Abstract : This study identifies dermal fibroblast microvesicles (extracellular vesicles) as efficient activators of dermal papilla cells and Norrin as a novel modulatory player in hair follicle physiopathology. Extracellular vesicles carrying frizzled ( Fzd4 ) receptors are secreted by activated dermal fibroblast to induce Norrin secretion by dermal papilla cells. In turn, Norrin activates follicular keratinocytes through its Fzd4 receptor provided by dermal fibroblast‐extracellular vesicles and enhances hair follicle growth.