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

Commun Biol. 2020 Apr 23;3(1):188. doi: 10.1038/s42003-020-0922-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Cell Communication
  • Cellular Senescence / genetics*
  • Female
  • Fibroblasts / metabolism*
  • Gene Expression Profiling*
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • RNA-Seq
  • Single-Cell Analysis*
  • Skin / cytology
  • Skin / metabolism*
  • Skin Aging / genetics*
  • Transcriptome*