Human Dermal Fibroblast Subpopulations Display Distinct Gene Signatures Related to Cell Behaviors and Matrisome

Abstract

Short title: Transcriptome analysis of dermal fibroblasts Abbreviations: ECM, extracellular matrix; Fp, papillary fibroblast; Fr, reticular fibroblast; Pn, number of cell passage. COL, collagen; MMP, matrix metalloproteinase Word count: 995 words

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

“…Furthermore, fibroblasts in cluster I express COL13A1 and COL23A1, two known markers of papillary fibroblasts (Haydont et al, 2019;Peltonen et al, 1999;Philippeos et al, 2018;Veit et al, 2011). High expression levels of another epidermal-dermal junction collagen gene, COL18A1, also supported the location of these fibroblasts within the papillary layer (Halfter et al, 1998;Haydont et al, 2019;Nauroy et al, 2017;Philippeos et al, 2018).…”

“…To better predict the potential localization of the four observed fibroblast populations within the dermis, we next studied the expression of sets of genes that have previously been related to papillary or reticular fibroblasts. While the most representative markers of the papillary fibroblasts comprise APCDD1, AXIN2, COLEC12, PTGDS and COL18A1, the reticular fibroblast signature is typically defined by a group of ten genes, including MGP or MFAP5 (Haydont et al, 2019;Janson et al, 2012;Nauroy et al, 2017;Philippeos et al, 2018) ( Figure S3). In agreement with the collagen expression data, our results showed that the papillary gene expression signature is mostly restricted to fibroblasts in cluster I ( Figures 2D and S3).…”

Deciphering the functional heterogeneity of skin fibroblasts using single‐cell RNA sequencing

“…Until now, skin FBs have been characterized as papillary and reticular FB. 5,8,10,12 Our analysis suggests a novel classification of dermal FB subsets, not solely due to their anatomical location within the skin, but, more importantly, based on their transcriptional signature. Interestingly, our newly identified FB subsets do not overlay with common markers used to identify papillary and reticular FBs, suggesting that FBs with similar functions are distributed over all dermal layers.…”

“…3,4 Based on their anatomical localization in the skin, two distinct populations of dermal FBs with different shape and function, that is, papillary and reticular FBs, have been identified. 1,[5][6][7][8][9][10] While the papillary dermis (uppermost 300 µm) displays high cell density, the reticular dermis is characterized by a dense ECM network and rather low cell density. 5 The majority of previous studies have investigated their functions in vitro, which strongly affects phenotype and function of FBs.…”

Reversion for correction: fibroblasts to the rescue!

“…Corrected and noncorrected fibroblasts were present in the revertant skin patch. It would be of interest to characterize these fibroblasts and see if the correction is associated with specific collagen VII producing fibroblast subpopulations or if it is also found in naturally low collagen VII expressing fibroblast subpopulations …”