Transcriptome landscape of myeloid cells in human skin reveals diversity, rare populations and putative DC progenitors

Background The heterogeneous functions of dermal myeloid cells in antigen presentation, and scavenging pathogens and cell debris places them centrally in cutaneous inflammation. Single cell transcriptomics can provide new understanding of the heterogeneity and function of yet incompletely understood human dermal myeloid cell subsets. Objective Investigate the transcriptome landscape of myeloid cells in healthy human skin. Methods Single cell RNA-sequencing was performed on skin biopsies from ten healthy donors and analyzed to identify myeloid cell populations. Results One LIN− HLA-DR+ cluster with expression of myeloid-specific genes was identified as a cluster of myeloid cells. Upon reanalysis of this cluster, we identified three macrophage subsets, marked by high expression of CCR1, MARCO or TREM2; and six dendritic cell subsets, marked by high expression of CLEC9A, CXorf21, MCOLN2, LAMP3, KIAA0101 and Langerin, representing respectively cDC1, two subsets of cDC2, a novel DC type, a cluster of proliferating DC, and a Langerhans cell subset. GO term analysis indicated specialized functions for the discrete rare populations of myeloid cells: TREM2 Mφ in lipid metabolism and LAMP3 DC as a mature cDC. Proliferating DCs appeared to represent cDC2 progenitors. Conclusion The transcriptional landscape of myeloid cell populations in human skin indicates several, novel populations with specialized functions, as well as a rare proliferating DC population that likely accounts for local regeneration or expansion of dermal DCs. We provide robust gene expression markers for each of these populations that should permit better understandings of their roles in various homeostatic and pathologic immune processes in the skin.