FP13 Endothelin-3 from the dermal papilla governs human hair fibre pigmentation
Jose Godoy Rodriguez, Leah Redmond, Min Waye Chew, Summik Limbu, Francisco Jimenez, Claire HigginsAbstract
Introduction and aims
Hair greying is one of the most visible hallmarks of ageing. This age-related phenomenon occurs as a result of disturbances in the two pathways concerning pigmentation within the hair follicle: melanogenesis, synthesis of melanin pigment within melanocytes; and melanin transfer, delivery of melanin granules to adjacent hair matrix keratinocytes, shaping the pigmented hair shaft. In the hair follicle, melanocytes are localized at the bottom of the hair bulb, proximal to the dermal papilla (DP), a structure known for coordinating hair growth and loss through paracrine signalling. We hypothesize that this proximity hints to the DP also playing a role in regulating hair pigmentation by paracrine secretions to neighbouring melanocytes.
Methods
Reanalysis of a human single-cell RNA sequencing whole-follicle dataset was performed using Seurat to identify crossmatching in pigmentation-related genes between cheetah and humans. CellChat was conducted to analyse potential receptor-ligand interactions between melanocytes and DP and validated by immunofluorescence staining. In vitro studies, using human melanocytes, were performed to assess the effect of identified ligands on pigmentation processes.
Results
Computational analysis showcased prominent expression of pigmentation-related genes in the human DP cluster, pointing to involvement of the DP in pigmentation modulation. Multiple ligand-receptor signalling pathways were established between melanocytes and DP using CellChat, underlining only one ligand exclusively secreted by the DP cluster, Endothelin (EDN)3, acting on the EDN receptor type B membrane receptor of melanocytes. Validating the computational data, Immunofluorescence staining in white and pigmented hair follicles validated the computational data and showed significantly higher EDN3 expression in the pigmented follicle DP. Treatment of cocultures of human melanocytes and keratinocytes with EDN3 led to a significant increase in melanin transfer into keratinocytes.
Conclusions
Our findings highlight the role of the DP in upregulating pigmentation by secretion of EDN3 to proximal melanocytes, which may lead to new therapeutic approaches for reversing or preventing hair greying.