A consensus single-cell transcriptomic atlas of dermal fibroblast heterogeneity

Single-cell RNA sequencing (scRNAseq) studies have unveiled large transcriptomic heterogeneity within both human and mouse dermal fibroblasts, but a consensus atlas that spans both species is lacking. Here, by studying 25 human and 9 mouse datasets through a semi-supervised procedure, we categorize 15 distinct human fibroblast populations across 5 main axes. Analysis of human fibroblast markers characteristic of each population suggested diverse functions, such as position-dependent ECM synthesis, association with immune responses or structural roles in skin appendages. Similarly, mouse fibroblasts were categorized into 17 populations across 5 axes. Comparison of mouse and human fibroblast populations highlighted similarities suggesting a degree of functional overlap, though nuanced differences were also noted: transcriptomically, human axes seem to segregate by function, while mouse axes seem to prioritize positional information over function. Importantly, addition of newer datasets did not significantly change the defined population structure. This study enhances our understanding of dermal fibroblast diversity, shedding light on species-specific distinctions as well as shared functionalities.