P39 Using single-cell transcriptomics to investigate the potential role of the human hair follicle dermal papilla in controlling hair fibre pigmentation

Abstract Introduction and aims The human dermal papilla (DP) is a population of cells located at the base of the hair follicle, which signals to surrounding matrix cells facilitating their incorporation into the layers of the hair fibre and the hair follicle. The DP controls the process of hair follicle induction, reflecting its critical role in orchestrating processes integral in hair growth. We hypothesize that distinct functional subgroups exist within the structure, which would mean that there are different types of DP cells within each follicle. Methods To begin testing this, we reanalysed the single-cell RNA sequencing (RNA-Seq) dataset of the human anagen hair follicle used in the 2022 study by Shim et al. To expand on this, we are now generating single-cell RNA-Seq datasets of patient-matched pigmented and nonpigmented hair follicles (n = 4 patients). These datasets will be used to explore heterogeneity in the human DP, and to investigate which subpopulations are potentially changed in the case of pigmentation loss. This will allow us to explore a potentially undiscovered role of the DP in controlling hair fibre pigmentation. Results We found four distinct subpopulations in the DP with statistically significant marker genes in the Shim dataset. This confirms transcriptional heterogeneity in the human DP, hinting at clusters of DP cells with specialized functions within each hair follicle. One subcluster, which expressed S100B, endothelin-3 and bone morphogenetic protein (BMP)4, was of particular interest and gene ontology analysis of the genes in this cluster revealed terms associated with skeletal development and BMP signalling. We hypothesize that this DP cluster regulates melanin transfer from bulbar melanocytes to neighbouring keratinocytes, owing to the known involvement of the mentioned genes in both melanogenesis and melanin transfer. Conclusions The human DP is a heterogeneic structure, with a potentially unexplored role in controlling hair fibre pigmentation.