Advances in cellular and spatial profiling technologies have rapidly expanded the understanding of fibroblast heterogeneity within the target tissues of disease. In 2025, there has been a shift towards a consensus definition of shared cross-tissue fibroblast states and a greater understanding of their molecular drivers and disease-relevant effector functions.
Key points
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Construction and analysis of a single-cell and spatial tissue atlas of human skin fibroblasts revealed shared disease-related fibroblast states, including two cross-tissue immune-interacting fibroblast states implicated in distinct inflammatory tissue pathologies in immune-mediated inflammatory diseases6.
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A CRISPR-based gene activation platform combined with single-cell RNA sequencing revealed key transcription factors that regulate disease-relevant fibroblast gene programs, including a ‘universal’ program that innately antagonizes the ‘inflammatory’ program, highlighting the therapeutic potential of fibroblast reprogramming7.
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Rheumatoid arthritis synovial fibroblasts that express MHC class II molecules demonstrate immunosuppressive functions via antigen presentation to T cells without co-stimulation, which limits T cell activation in the joint, adding to the emerging body of evidence of the regulatory roles of fibroblasts in inflammatory diseases8.
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Croft, A.P., Hackland, A. Fibroblast heterogeneity in 2025. Nat Rev Rheumatol 22, 86–88 (2026). https://doi.org/10.1038/s41584-025-01345-3
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DOI: https://doi.org/10.1038/s41584-025-01345-3
