Description

Comparative spatial transcriptomic and single-cell analyses of human nail units and hair follicles demonstrate transcriptional similarities between the onychodermis and follicular dermal papilla. The nail unit and hair follicle are both hard keratin-producing organs that share various biological features. Here we used a Digital Spatial Profiling (DSP) and single cell RNA sequencing (scRNA-seq) to define a spatially resolved expression profile of the human nail unit and hair follicle. Our approach demonstrated the presence of a nail-specific mesenchymal population called onychofibroblasts within the onychodermis. Onychodermis and follicular dermal papilla (DP) both expressed WNT and bone morphogenetic protein (BMP) signaling molecules. In addition, nail matrix epithelium and hair matrix showed very similar expressions profile, including expression of hard keratins and HOXC13, a transcriptional regulator of the hair shaft. Integration of scRNA-seq and DSP data via computational deconvolution methods estimated epithelial and mesenchymal cell abundance in the nail- and hair-specific regions of interest and revealed close transcriptional similarity between these major skin appendages. To analyze the function of BMPs in nail differentiation, we treated cultured human nail matrix keratinocytes (NMKs) with BMP5, which are highly expressed by onychofibroblasts. We observed increased expressions of hard keratin and its regulator genes such as HOXC13. Collectively, our data suggest that onychodermis is the counterpart of DP and that BMP5 in onychofibroblasts play a key role in differentiation of NMKs.