(A) UMAP of 8,860 skin fibroblasts (4,893 jSSc and 4,893 healthy) identifying 11 transcriptionally distinct subclusters by marker gene expression. (B) UMAP of 2,719 macrophages (852 jSSc and 1,867 healthy) identifying 10 annotated subclusters. (C) Bar plot of fibroblast and macrophage subcluster proportions in jSSc versus healthy samples. (D) CellChat analysis of TGFB ligand-receptor interactions between fibroblast and macrophage subtypes in jSSc (left) and healthy (right) skin, showing expanded intercluster connectivity in jSSc; numbered clusters denote fibroblasts, unnumbered denote macrophages. (E) Schematic of a macrophage-driven profibrotic circuit: macrophage-derived TGFB, FGF, and IGF activate fibroblast ECM programs via WNT signaling, while NOTCH and TNF reinforce chronic fibroblast activation. (F) NicheNet interaction heatmap highlighting signaling from MMP19⁺CTSL⁺ macrophages to ANGPTL7⁺ fibroblasts via ligands (TGFB1, AREG, and COL6A2) and receptors (TGFBR1, FGFR1, and FZD9I). (G) Spatial transcriptomics showing macrophage-fibroblast colocalization (<25 μm) in jSSc skin; insets highlight high-resolution regions in the reticular dermis, perivascular infiltrate region. (H) Marker genes of STC1⁺FZD9⁺, ANGPTL7⁺, and SFRP2⁺SFRP4⁺ were significantly upregulated in the fibroblasts that colocalized with macrophages compared with non-colocalized fibroblasts (P < 1 × 10^–5 using the Wilcoxon rank-sum test; Bonferroni-adjusted P < 0.05). (I) Spatial localization of STC1⁺FZD9⁺, ANGPTL7⁺, and SFRP2⁺SFRP4⁺ fibroblasts in the same biopsy region as shown in G.