2024/12/28 by Yinan Li, Tim Filla, Andrea‐Hermina Györfi +15 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Cutaneous Melanoma Detection and Management #Skin and Cellular Biology Research #Systemic Sclerosis and Related Diseases
paper · pdf · doi:10.1101/2024.12.28.630505
openalex publication_date 2024/12/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Abstract Spatially non-resolved transcriptomic data identified functionally distinct populations of fibroblasts in health and disease. However, in-depth transcriptional profiling in situ at single-cell resolution has not been possible so far. Here, we studied fibroblast populations in the skin of SSc patients and healthy individuals using cyclic in situ hybridization (cISH) as a novel approach for spatially-resolved transcriptional phenotyping with subcellular resolution. cISH deconvoluted the heterogeneity of 20,979 cells including 3,764 fibroblasts (FB). BANKSY-based spatially-informed clustering identified nine FB subpopulations, with SFRP2+ RetD FB and CCL19+ nonPV FB as novel subpopulations that reside in specific cellular niches and display unique gene expression profiles. SFRP2+ RetD FB and CCL19+ nonPV FB as well as COL8A1+ FB, display altered frequencies in SSc skin and play specific, disease-promoting roles for extracellular matrix release and leukocyte recruitment as revealed by their transcriptional profile, their cellular interactions and ligand-receptor analyses. The frequencies of COL8A1+ FB and their interactions with monocytic cells and B cells are associated with progression of skin fibrosis in SSc. In summary, our spatially-resolved transcriptomic approach identified novel fibroblast subpopulations deregulated in SSc skin with specific pathogenic roles, some of which may potentially serve as biomarkers for progression of skin fibrosis.