Fig. 4: DNMT3A CHIP promotes diffuse cardiac fibrosis in mice with DNMT3AR882H bone marrow cells.

a Schematic illustration of the experimental design of the in vivo study. b ELISA-based quantification of cardiac troponin in serum of wild-type mice transplanted with wild-type bone marrow cells (WT) and wild-type mice transplanted with DNMT3AR882H bone marrow cells (DNMT3AR882H) (n = 5 biologically independent samples). Source data are provided as a Source Data file. c, d Picrosirius red staining of murine cardiac cross sections. c Infarct fibrotic scar in WT and DNMT3AR882H mice. d Remote zone in WT and DNMT3AR882H mice. e Quantification of the fibrotic score for the scar and (f) for the remote zone (n = 5 biologically independent samples). Source data are provided as a Source Data file. g Representative uniform manifold approximation and projection (UMAP) plots of scRNA-seq sequenced WT and DNMT3AR882H murine hearts after AMI (day 75) showing different cell clusters identified after annotation. CM Cardiomyocytes; EC Endothelial cells; FB Fibroblasts; PC Pericytes (n = 3 biologically independent samples). h Dot plot depicting expression of fibrosis-related genes in the cardiac fibroblast cluster in the sequenced WT and DNMT3AR882H murine hearts after AMI (n = 3 biologically independent samples). i Mean expression of Col3a1, Postn, Pdgfra in WT and DNMT3AR882H murine hearts after AMI (n = 3 biologically independent samples). Source data are provided as a Source Data file. j Mean expression of Ccr2 in WT and DNMT3AR882H murine hearts after AMI (n = 3 biologically independent samples). Source data are provided as a Source Data file. Data are shown as mean ± SEM. b, e, f, i, j Normal distribution was assessed using the Shapiro–Wilk test. b, e, f, i, j. Statistical analysis was performed using unpaired, two-sided Student’s t tests. (b, e, f, i, j. t = 0.917, 8 degrees of freedom (b); t = 0.418, 8 degrees of freedom (e); t = 3.027, 8 degrees of freedom (f); t = 3.434, 4 degrees of freedom; t = 5.024, 4 degrees of freedom; t = 4.966, 4 degrees of freedom (i); t = 5.003, 4 degrees of freedom (j).