Molecular Signatures and Signaling Interactions of the Hair Follicle Stem Cell Niche

Signaling interactions between the dermal papilla (DP) and neighboring stem cells in the hair germ (HGSCs) and bulge (BuSCs) regulate new follicle growth in the hair cycle. To study these interactions, the three populations had been profiled together by now-outdated microarrays or separately by bulk RNA-sequencing. Recent single-cell transcriptomics established signatures of DP, BuSCs and HGSCs, but low detection sensitivity limited the depth of gene expression discovery. Here, we define the transcriptomes of DP, BuSCs, HGSCs, epidermal, follicle and dermal fibroblast cells – after flow-sorting each population from four neighboring mouse back skin regions – to gain deeper insights into the unique gene expression programs of SCs and their instructive niche. With cross-comparisons of 56 whole-transcriptome measurements, we classify cell type-specific molecular signatures of enriched genes with unprecedented sensitivity. Joint analysis with signatures from 15 leading studies published in the last 20 years revealed many previously undescribed DP, BuSC and HGSC genes in mouse and human counterparts. With ligand-receptor mapping and CellChat analyses we then uncover comprehensive cell-cell communication insights. Finally, we provide a new installment of our Hair-Gel repository along with numerous signature and other gene tables for easy exploration of gene expression in hair follicle SCs and their niche.