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

• DOI: 10.1096/fj.201902001rr
• Publication Date: 2020-01-13T05:20:04Z
• Authors: Vera Vorstandlechner; Maria Laggner; Polina Kalinina; Werner Haslik; Christine Radtke; Lisa Shaw; Beate Maria Licht...; Erwin Tschachler; Hendrik Jan Anker...; Michael Mildner
• Keywords: Reticular connective tissue; Human skin; Reticular Dermis; Papillary dermis

Though skin fibroblasts (FB) are the main cell population within dermis, different FB subsets not well characterized and traditional classification into reticular papillary FBs has little functional relevance. To fill gap of knowledge on diversity in human skin, we performed single-cell RNA sequencing. Investigation marker genes for subtypes revealed a heterogeneous picture FBs. When mapping markers, could detect cluster specificity, suggesting that these two populations show higher transcriptional heterogeneity than expected. This finding was further confirmed by situ hybridization, showing DPP4 expressed both dermal layers. Our analysis identified six clusters with distinct signatures. Importantly, demonstrate DPP4+ producers factors involved extracellular matrix (ECM) assembly. In conclusion, provide evidence hitherto considered markers ideal to characterize subpopulations sequencing analyses. The identification as ECM-producing cells will foster development anti-fibrotic treatments other organs.