(A) UMAP re-clustering of fibroblast population. (B) Gaussian kernel density estimation of cells within the fibroblast cluster across the indicated genotypes. (C) Heatmap of top 25 differentially expressed genes in the fibroblast cluster between WT and Dsg2^mut/mut mice with sideby-side comparison of the expression of those same genes from Dsg2^mut/mut × Ccr2^–/– mice. Example genes are annotated. (D) Z-score feature plot, overlaying a fibroblast gene signature derived from the heatmap in C (genes listed to the side) and displayed on the fibroblast UMAP projection, split by genotype. (E) Graph of Z-score values for fibroblast gene signature derived from heatmap in C compared across genotypes. Data presented as a box-and-whisker plot. The 5 number summary (minimum, 25% IQR, median, 75% IQR, and maximum) as well as total number of values for each group is provided as follows; WT: –0.7450, –0.4597, –0.2805, –0.07749, 0.9996, n = 1717; Dsg2^mut/mut: –0.6437, –0.008809, 0.2165, 0.4886, 1.611, n = 1675; Dsg2^mut/mut × Ccr2^–/–: –0.7450, –0.2865, –0.06280, –0.2262, 1,371, n = 2625. P values inset and determined by 1-way ANOVA. (F) Top GO Biological pathways for the top 25 differentially upregulated genes in WT versus Dsg2^mut/mut mice (red) and WT versus Dsg2^mut/mut × Ccr2^–/– mice (blue) (derived from C). (G) Representative immunostained myocardium displaying colocalization of CCR2⁺ macrophages (green) with Periostin⁺ (PostN⁺) fibroblasts (red) at 16 weeks of age. Scale bars: 60 μm. (H) Representative immunostained myocardium depicting PostN⁺ (red) areas via immunofluorescence staining from mice aged 16 weeks from indicated genotypes. Scale bars: 40 μm. (I) Quantification of PostN⁺ area as a percentage of total area in mice of the indicated genotypes (P values inset, determined via 1-way ANOVA); WT (n = 5); Dsg2^mut/mut (n = 4); and Dsg2^mut/mut × Ccr2^–/– (n = 4). Data presented as mean ± SEM, n = 4 per cohort, P values inset and determined via 1-way ANOVA.