Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming.
Llorenç Solé-Boldo, Günter Raddatz, Sabrina Schütz, Jan-Philipp Mallm, Karsten Rippe, Anke S Lonsdorf, Manuel Rodríguez-Paredes, Frank Lyko
Author Information
- Llorenç Solé-Boldo: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany. ORCID
- Günter Raddatz: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany.
- Sabrina Schütz: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany.
- Jan-Philipp Mallm: Division of Chromatin Networks, German Cancer Research Center and Bioquant, 69120, Heidelberg, Germany.
- Karsten Rippe: Division of Chromatin Networks, German Cancer Research Center and Bioquant, 69120, Heidelberg, Germany. ORCID
- Anke S Lonsdorf: Department of Dermatology, University Hospital, Ruprecht-Karls University of Heidelberg, 69120, Heidelberg, Germany.
- Manuel Rodríguez-Paredes: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany. m.rodriguez@dkfz.de. ORCID
- Frank Lyko: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany. f.lyko@dkfz.de.
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.
Adult
Age Factors
Aged
Aged, 80 and over
Cell Communication
Cellular Senescence
Female
Fibroblasts
Gene Expression Profiling
Humans
Male
Middle Aged
Phenotype
RNA-Seq
Single-Cell Analysis
Skin
Skin Aging
Transcriptome
