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[Preprint]. 2025 Jan 31:rs.3.rs-5875531. [Version 1] doi: 10.21203/rs.3.rs-5875531/v1

Figure 5. Phenotypic shifts and the emergence of disease-associated fibroblasts in IHD.

Figure 5.

a, Expression of characteristic marker genes in each identified cell population. b, UMAP clustering based on marker gene expression for control and IHD heart tissues after QC, data filtering, and Harmony integration. c, Relative proportion of different cardiac cell types for control and IHD samples. d-e, Unsupervised sub-clustering of cardiomyocytes and fibroblasts identifies 19 unique clusters within the integrated dataset across control (d) Control and IHD cardiomyocytes (e). f-g, Expression of cardiomyocyte and fibroblast marker genes across these 19 clusters in control (f) and IHD (g) samples. Three clusters (9, 10, and 11) that predominantly express cardiomyocyte markers in the control heart shift to expressing fibroblast markers in the IHD heart (fibrotic-cardiomyocyte). h, Identified cardiomyocyte, fibrotic-cardiomyocyte, and fibroblast populations in control and IHD heart. i, Relative proportion between cardiomyocytes and fibroblasts in control and ischemic heart samples. IHD individuals showed decreased proportions of cardiomyocytes and increased proportions of fibroblasts (P = 0.021, two-tailed Wilcoxon test). j, Average metagene (as listed in Supplementary Table 9) expression in clusters 9 and 11 from control and IHD samples, indicating downregulation of cardiomyocyte genes, upregulation of fibroblast, hypoxia, and collagen genes. Statistical significance was evaluated using a two-sided Wilcoxon test. k, Immunohistochemistry using Sirius red staining; collagen fibers in red and muscle fibers in yellow.