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• W3202380493 abstract "Abstract Objectives Although the role of the CSF1/CSF1R axis in pigmented villonodular synovitis (PVNS) has been confirmed, the cells that express CSF1 and CSF1R and the underlying mechanism remain unclear. Single-cell RNA sequencing (scRNA-seq) of PVNS obtained through biopsies depicted the cellular diversity of PVNS, revealed specific CSF1/CSF1R-expressing cells and further identified novel gene expression that is associated with the development of PVNS. Methods scRNA-seq was performed on tissues obtained from the 6 biopsies of 3 patients with PVNS. Flow cytometry, immunofluorescence and western blot validated the transcriptional results, while co-culture systems revealed the cross talk between fibroblasts and macrophages. Results 8 subsets of fibroblasts and 5 subsets of macrophages were identified from the synovium of patients with PVNS and were found to be related to distinct signaling pathways. The cellular components of localized and diffuse PVNS are overall similar. Moreover, the synovium and nodule of PVNS share similar composition. The specific cells expressing CSF1/CSF1R were also identified. Other than that, unique CXCL12 + CSF1 + fibroblasts were revealed to attract macrophages as disease-causing synovial fibroblasts, leading to the formation of masses in PVNS. Conclusions PVNS consists of macrophages, fibroblasts, T cells, endothelial cells and mast cells. Among them, the CSF1-expressing fibroblasts appeared to be tumor-like cells that attract macrophages, subsequently forming tumor-like mass in PVNS. This paves the path for novel treatments of PVNS by targeting CXCL12 + CSF1 + fibroblasts and the CXCL12-CXCR4 axis." @default.
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• W3202380493 date "2021-10-01" @default.
• W3202380493 modified "2023-09-26" @default.
• W3202380493 title "Single-cell RNA-seq analysis reveals aberrant CSF1 expression in disease-causing synovial fibroblasts of pigmented villonodular synovitis" @default.
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• W3202380493 doi "https://doi.org/10.1101/2021.09.29.462128" @default.
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