Fig. 2. Single-cell atlas of mouse atria.

(A) HOMER mice are exposed to mitral valve regurgitation (MR), high-fat diet (HFD), and angiotensin 2 (Ang2). (B) Doppler of MR. (C) (Left) MRI of left atrium (LA). Scale bars, 3 mm. (Right) LA end-systolic volume, n = 6 to 10 per group from two independent experiments, two-tailed Mann–Whitney test. (D) AFib inducibility and burden. n = 8 to 12 per group from two independent experiments. (Left) Two-sided Fisher’s exact test. (Right) Two-tailed Mann–Whitney test. Other parameters are shown in table S7. SR, sinus rhythm. (E) scRNA-seq was performed in four sham and four HOMER mice. (F) (Left) UMAP. (Right) Cell population distributions. (G) Log₂(FC) of cell abundance in mouse and human atria. (H) Flow cytometry of sham and HOMER atria. n = 21 per group from five independent experiments, two-tailed Student’s t test. APC/Cy7, allophycocyanin/cyanine 7; PE/Cy7, phycoerythrin/cyanine 7. (I) Scatterplot showing C5 GOBP GSEA species concordance. GSEA is performed on lists of genes ranked according to differential expression in the disease state. −log₁₀(FDR) is plotted for mouse (x axis) and human (y axis). −log₁₀(FDR) are negative if the gene set is down-regulated. Yellow indicates high and blue indicates low gene set density. (J) Genes in MP/DC cluster ranked according to log₂(FC) between four HOMER and four sham mice. The y axis was broken at −5 for displaying the top down-regulated genes. (K) Subclustering of MP/DCs from four sham and four HOMER mice. APC, antigen-presenting cell. (L) Atrial Spp1⁺ macrophages by scRNA-seq. n = 4 per group, two-tailed Student’s t test. (M) Gene expression levels (represented by log-transformed normalized counts) across macrophage clusters. (N) Spp1 expression in MP/DCs from sham and HOMER mice. (O) Spp1⁺ subpopulations in sham and HOMER mice. n = 4 per group, two-tailed Student’s t test. non-CM, noncardiomyocyte. (P) Flow cytometry of atrial macrophages in sham and HOMER mice. n = 6 to 7 per group from two independent experiments, two-tailed Student’s t test. PerCP/Cy5.5, peridinin-chlorophyll-protein/cyanine 5.5. All bar graph data are mean ± SEM with individual values for data distribution.