Molecular signatures and signaling interactions of the hair follicle stem cell niche.

Signaling interactions between the dermal papilla and neighboring stem cells (SCs) in the hair germ and bulge regulate new follicle growth in the hair cycle. To study these interactions, the 3 populations had been profiled together by now-outdated microarrays or separately by bulk RNA sequencing. Recent single-cell transcriptomics established signatures of dermal papilla, bulge SCs, and hair germ SCs, but low detection sensitivity limited the depth of gene expression discovery. In this study, we define the transcriptomes of dermal papilla cells, bulge SCs, hair germ SCs, epidermal and follicle epithelial cells and dermal fibroblasts-after flow sorting each population from 4 neighboring mouse back skin regions-to gain deeper insights into the unique gene expression programs of hair follicle 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 dermal papilla, bulge SC, and hair germ SC genes in mouse and human counterparts. With ligand-receptor mapping and CellChat analyses, we then uncover comprehensive cell-cell communication insights. Finally, we provide our transcriptome data in a full update 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.