Fibroblasts are an essential cell population for human skin architecture and function. While fibroblast heterogeneity is well established, this phenomenon has not been analyzed systematically yet. We have used single-cell RNA sequencing to analyze the transcriptomes of more than 5,000 fibroblasts from a sun-protected area in healthy human donors. Our results define four main subpopulations that can be spatially localized and show differential secretory, mesenchymal and pro-inflammatory functional annotations. Importantly, we found that this fibroblast ‘priming’ becomes reduced with age. We also show that aging causes a substantial reduction in the predicted interactions between dermal fibroblasts and other skin cells, including undifferentiated keratinocytes at the dermal-epidermal junction. Our work thus provides evidence for a functional specialization of human dermal fibroblasts and identifies the partial loss of cellular identity as an important age-related change in the human dermis. These findings have important implications for understanding human skin aging and its associated phenotypes.
CITATION STYLE
Solé-Boldo, L., Raddatz, G., Schütz, S., Mallm, J. P., Rippe, K., Lonsdorf, A. S., … Lyko, F. (2020). Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming. Communications Biology, 3(1). https://doi.org/10.1038/s42003-020-0922-4
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