Dokument: Spatially informed phenotyping by cyclic-in-situ-hybridisation identifies novel fibroblast populations and their pathogenic niches in systemic sclerosis
| Titel: | Spatially informed phenotyping by cyclic-in-situ-hybridisation identifies novel fibroblast populations and their pathogenic niches in systemic sclerosis | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=71881 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20260114-131106-2 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Li, Yi-Nan [Autor] Filla, Tim [Autor] Györfi, Andrea-Hermina [Autor] Liang, Minrui [Autor] Devakumar, Veda [Autor] Micu, Alexandru [Autor] Chai, Hongtao [Autor] Homey, Bernhard [Autor] Dietrich, Sascha [Autor] Distler, Jörg H.W. [Autor] | |||||||
| Dateien: |
| |||||||
| Beschreibung: | Objectives
Spatially nonresolved transcriptomic data identified several functionally distinct populations of fibroblasts in health and disease. However, in-depth transcriptional profiling in situ at the single-cell resolution has not been possible so far. We thus aimed to profile these populations by single-cell spatial transcriptomics using cyclic in situ hybridisation (cISH). Methods We studied fibroblast subpopulations in the skin of systemic sclerosis (SSc) patients and heathy individuals using cISH as a novel approach for transcriptional phenotyping with subcellular resolution. Clustering was performed using Building Aggregates with a Neighbourhood Kernel and Spatial Yardstick (BANKSY) as a novel approach for spatially informed transcriptional phenotyping. The findings were further validated by integration with single-cell RNA sequencing in distinct SSc cohorts. Results BANKSY-based spatially informed clustering identified 9 fibroblast (FB) subpopulations, with SFRP2+ reticular dermis (RetD) FB and CCL19+ nonperivascular (nonPV) FBs as novel subpopulations that reside in specific cellular niches and display unique gene expression profiles. SFRP2+ RetD FBs and CCL19+ nonPV FBs as well as COL8A1+ FBs 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+ FBs and their interactions with monocytic cells and B cells are associated with the progression of skin fibrosis in SSc. Conclusions Our cISH-based, spatially resolved transcriptomic approach identified novel fibroblast subpopulations deregulated in SSc skin with specific pathogenic roles. COL8A1+ FBs and their immune interactions may also have potential as biomarkers for future progression of skin fibrosis. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Li, Y.-N., Filla, T., Györfi, A.-H., Liang, M., Devakumar, V., Micu, A., Chai, H., Bergmann, C., Pecher, A.-C., Henes, J., Moinzadeh, P., Al-Gburi, S., Krieg, T., Kreuter, A., Wang, J., Schett, G., Homey, B., Dietrich, S., Distler, J., & Matei, A.-E. (2025). Spatially informed phenotyping by cyclic-in-situ-hybridisation identifies novel fibroblast populations and their pathogenic niches in systemic sclerosis. Annals of the Rheumatic Diseases, 84(11), 1852–1864. https://doi.org/10.1016/j.ard.2025.06.002 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 14.01.2026 | |||||||
| Dateien geändert am: | 14.01.2026 |
