In single-cell RNA sequencing, activated signaling pathways were largely different between SSc and RA synovial fibroblasts with enrichment in TGF and interferon pathways in SSc. To provide a comprehensive atlas of cell populations and activated pathways in the SSc synovium: Single cell RNA sequencing will be analyzed to characterize the phenotype of synovial cells and activated pathways in SSc versus RA. Using bioinformatics packages, we will also analyze and visualize communication and cell-cell interactions in SSc synovium. Activated pathways and cell-cell interactions will be confirmed by immunohistochemistry in synovial tissues. Specific functions and cell-cell interaction will be assessed in 3D culture. This work will allow, for the first time, a detailed characterization of synovitis in SSc at the cellular and molecular levels.
Project LeadMuriel Elhai
(i) establish a comprehensive atlas of cell populations and pathways activated in the SSc synovium
(ii) characterize the biology of SF in SSc
(iii) identify potential drivers of cellular activation in SSc arthritis.
Milestone 2: Analysis of the cytokines/chemokines driving the phenotype of SSc SF (M12-M 18)
Milestone 3: Manuscript about synovitis in SSc at tissue and cellular levels (M15-M21)
Milestone 4: Analysis of functional changes characterizing SSc SF(M12-M24)
Milestone 5: Identification of therapeutic targets in SSc arthritis (M18-M30)
Milestone 6: Manuscript about therapeutic targets in SSc arthritis(M30-M36)
Milestone 7: Training of patients research partners (M6) and regular meetings every 3 months
Three SSc patients are involved in this project, two have undergone synovial biopsy and one is a member of the Swiss Scleroderma Association responsible for the Berne group. A patient journalist was consulted to improve the synovial biopsy protocol and to write the lay summary. Regular meetings with patients are organised to better target the needs and expectations of patients and to improve the visibility of the project. They will visit the laboratory on 16 September 2022 as part of the open day for patients and will receive research training in collaboration with the USZ clinical trials centre in early 2023.
As part of this funding, the first results and perspectives were presented to the French patients at the ASF medical day and will be presented to the Swiss patients next year.
A report will be written, which will be published in the Scleroderma Patient Journal. These oral and written presentations allow patients to be informed about the progress and results of the project, to give their opinion and to contact us later if necessary (contact details provided).