Fig. 2: Cardiac fibroblast-mediated regulation of BMP4 availability in the inflamed myocardium.
a,b,i–l, sc-RNA-seq analysis of sorted CD45−PDPN+CD31− cardiac fibroblasts isolated from 4-week-old and 8-week-old control or TCRM mice. a, UMAP representation showing 10 cell clusters depicting cardiac fibroblast heterogeneity (top) and condition (bottom). b, Projection of the indicated gene expression on cardiac fibroblast UMAP plot from control and TCRM mice. c,d, Ccl2 (c) and Il6 (d) mRNA expression in sorted cardiac fibroblasts of 8-week-old control or TCRM mice. e–h, Multi-parametric flow cytometric analysis of surface expression of CD157 (e), NCAM (f), SCA-1 (g) and ICAM1 (h) by cardiac fibroblasts from control or TCRM mice. MFI of the indicated activation markers in CD45−PDPN+CD31− cardiac fibroblasts. Dots represent values from individual mice;box plots as in Fig. 1. i, Diffusion map representation based on gene expression in cardiac fibroblasts colored according to heterogeneity (top) and origin (bottom). j,k, Projection of the indicated gene signatures onto diffusion maps. l, Expression profile of Bmp4 in cardiac fibroblast subsets shown as violin plots. m,n, Representative confocal microscopy analysis of hearts from control (m) and TCRM (n) mice using the indicated markers. Single-cell transcriptomics data represent a total of 65,545 cardiac fibroblasts from control (n = 4) and TCRM (n = 5) mice. Pooled data from 2–3 independent experiments with n = 6 mice per group (c) or n = 9, 6 and 6 mice per group (d–h). Representative sections from one out of five control or TCRM mice (m,n). Statistical analysis was performed using two-tailed Student’s t-test (c,d) or one-way ANOVA with Tukey’s multiple comparisons test (e–h) with *P < 0.05, **P < 0.01 and ***P < 0.001.
