Single-cell transcriptomes of the aging human skin reveal loss of fibroblast priming

Fibroblasts are the main dermal cell type and are essential for the architecture and function of human skin. Important differences have been described between fibroblasts localized in distinct dermal layers, and these cells are also known to perform varied functions. However, this phenomenon has not been analyzed comprehensively yet. Here we have used single-cell RNA sequencing to analyze >15,000 cells from a sun-protected area in young and old donors. Our results define four main fibroblast subpopulations that can be spatially localized and functionally distinguished. Importantly, intrinsic aging reduces this fibroblast ‘priming’, generates distinct expression patterns of skin aging-associated genes, and substantially reduces the interactions of dermal fibroblasts with other skin cell types. Our work thus provides comprehensive evidence for a functional specialization of human dermal fibroblasts and suggests that the age-related loss of fibroblast priming contributes to human skin aging. Overall 5 samples were analyzed. Two of them are from young subjects (y1=25y, y2=27y) and serve as replicates, three of them are from old subjects (o1=53y, o2=70y, o3=69y) and serve as replicates. Please note that the 'seurat_analysis_lyko.RData' file was replaced with the seurat_analysis_lyko.rds on Aug 6th, 2020.