Fig. 6: Regulation of BMP4 expression in human myocardial inflammatory disease.
a–k, snRNA-seq from left or right ventricular EMBs from patients with acute myocarditis (AM) (n = 5), inflammatory cardiomyopathy (ICM) (n = 8), dilated cardiomyopathy (DCM) (n = 3) or undergoing heart transplantation (HTx) (n = 7). a,b, UMAP representation (a) and abundance of cardiac cell populations (b) in individual patients. c–e, Frequencies of T cells (c), inflammatory macrophages (d) and cardiomyocytes (e) in patients stratified according to high (>6%, T cellHigh, n = 7), intermediate (3–6%, T cellInt, n = 9) and low (<3%, T cellLow, n = 7) proportions of heart-infiltrating T cells. Dots indicate individual patients; bars indicate geometric means. f, Correlation between T cells and inflammatory macrophages (left) and T cells and resident macrophages (right). g, Heat maps showing average gene expression of the indicated, differentially expressed genes grouped by function in T cells, macrophages and cardiomyocytes. h, Significantly enriched pathways according to GO enrichment analysis based on differentially expressed genes between cardiac fibroblasts from T cellLow and T cellHigh cardiac biopsies. i, Average BMP4 gene expression in cardiac fibroblast. Dots indicate values of individual patients; box plots as in Fig. 1. j, ELISA-based quantification of BMP4 concentration in serum from healthy donors or patients with biopsy-confirmed and/or cardiac MRI-confirmed acute myocarditis. Dots indicate values of individual patients; data are mean ± s.e.m. k, ROC curve of BMP4 serum concentrations of patients with acute myocarditis and healthy controls. snRNA-seq data represent a total of 44,114 nuclei, two biopsies per patient (n = 23 patients). Statistical analysis was performed using one-way ANOVA with Dunnett’s post test (c–e), Benjamini, Krieger and Yekutieli post test (i) or Mann–Whitney U-test (k) with **P < 0.01 and ***P < 0.001. Simple linear regression test was used in f. CI, confidence interval; LEC, lymphatic endothelial cells; NC, neural cells; SMC, smooth muscle cells.
