Exosomal miR-199a-3p From Dermal Papilla Cells Regulates Hair Follicle Pigmentation by Targeting POU2F1 in Melanocytes.

To elucidate the paracrine regulatory mechanism of dermal papilla cells (DPCs) on melanocyte (MC) melanogenesis, we focused on exosomal miR-199a-3p as a key mediator. DPCs, MCs, and DPC-Exos were identified by immunofluorescence, Western blot (WB), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). Functional assays showed DPC-Exos were internalized by MCs, enhanced proliferation, decreased apoptosis, and elevated melanin production. miRNA sequencing identified miR-199a-3p as the key exosomal cargo, which was localized to hair follicle bulbs by fluorescence in situ hybridization (FISH). Transwell co-culture and Cy3-tracing revealed intercellular transfer. Dual-luciferase assays confirmed miR-199a-3p directly targets the 3'UTR of POU2F1. Additionally, exosomal miR-199a-3p promoted the growth of ex vivo hair follicles and significantly regulated the expression of melanogenesis-related genes in hair follicles. Gain-of-function experiments demonstrated that DPC-Exos transfected with miR-199a-3p mimics suppressed POU2F1, effectively reversing its anti-melanogenic activity. This study elucidates an exosome-mediated DPC-MC regulatory axis centered on miR-199a-3p/POU2F1, providing novel therapeutic targets for pigmentation disorders and advancing animal coat color modulation strategies.