Fig. 3

Fibroblast subpopulations in ARVC human hearts. A UMAP embedding of eight fibroblast subpopulations. B Dot plot showing the top five marker genes of each subcluster. Dot color and size correspond to the expression of each gene and the proportion of cells expressing each gene, respectively. C The top five enriched GOBP of each cluster. D The ratio of each subcluster in the different phases and topographic regions. E Trajectory analysis of selected fibroblast clusters based on Slingshot. F RNA velocity of fibroblast clusters. G Density plots reflecting the number of FB cells along the lineage FB0 stratified for different phases and topographic regions. H Predicted expression of genes showing interesting patterns based on a negative binomial generalized additive model (NB-GAM) for each gene across pseudotime in patient AC_LV_4 (left) and patient AC_RV_3 (right). Normalized expression is smoothed expression from NB-GAM scaled to the maximum value for each gene. I Multiple labeling staining for TNMD⁺ VIM⁺ fibroblasts; scale bar indicates 100 μm. Each spot represents one sample. Data are mean ± SD. Mann–Whitney U test was performed to compare the cellular ratio of TNMD⁺ VIM⁺ fibroblasts between ARVC and NC. FAP, fibro-adipogenic progenitor; FB, fibroblast; ARVC, arrhythmogenic right ventricular cardiomyopathy; NC, normal control; AC_LV, left ventricle of ARVC; AC_RV, right ventricle of ARVC; NC_LV, left ventricle of NC; NC_RV, right ventricle of NC; AC_PBMC, PBMC of ARVC. Gene names mentioned in the main text were color-coded