Development of a multi-organ single-cell atlas of systemic sclerosis reveals shared and tissue-specific pathogenic pathways.

An integrated multi-organ single-cell atlas of systemic sclerosis across skin, lung, synovium, and peripheral blood identifies recurrent ECM remodelling and interferon programmes plus a shared SFRP2+ myofibroblast subpopulation.

• Why it matters: Systemic sclerosis lacks broadly effective disease-modifying therapies, and it is unclear which transcriptional programmes are shared versus organ-specific across immune and fibroblast compartments.
• What they did: The authors integrated single-cell RNA-seq from six studies (401,902 cells, 90 individuals) using Harmony, then applied pseudobulk differential expression and gene set enrichment with reclustering of lymphoid, myeloid, and fibroblast populations.
• The result: Disease-associated programmes are strongly tissue dependent, yet ECM remodelling recurs in lung, skin, and synovium and interferon signalling recurs in skin, synovium, and peripheral blood mononuclear cells, enabling multi-organ target discovery.

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