Fig. 7: Identification of a CD9⁺ reparative like fibroblast population.

A A reparative cardiac fibroblast signature was generated using the top 25 DEGs of a reparative cardiac fibroblast cluster (as defined by Ruiz-Villalba et al.) vs. other fibroblasts in Ruiz-Villalba et al. Each cardiac fibroblast cluster from the CI population was scored with this signature and displayed in the heatmap. B Fibroblast clusters were assigned as “reparative” or “other” based on their relative enrichment of the reparative signature in (A). DEGs were computed between these two groups in the CI organoids and pathway enrichment analysis was performed (gProfiler, GO: Biological Processes). The enrichment score (−log₁₀ of adjusted p-value) of the top pathways in each group are displayed. C Violin plots showing expression of CD9 in human cardiac fibroblasts in healthy hearts and ischemic failing hearts (coronary HF (cHF)) (single cell dataset published in Wang et al.). D Upper; Representative flow cytometry analyses of CD9 expression in the CD90⁺ cardiac fibroblast population in the control and CI organoids. Lower; Quantification of the proportion of CD9⁺ cells in the CD90⁺ cardiac fibroblast population in the control and CI organoids (N = 3 biologically independent samples). RT-qPCR expression analyses of indicated genes in the CD9⁺ and CD9^- cardiac fibroblast populations isolated (FACS) from the CI organoids (N = 3 biologically independent samples). F Schematic summary of cardiac organoid modeling detailing the heterogeneity of canonical and reparative like fibroblasts observed in the cardiac injury conditions. CF cardiac fibroblast, VCM ventricular cardiomyocyte, CI organoid cardiac injury organoid. Statistical analysis was performed by two-sided unpaired t-test in (C)–(E). All error bars represent SEM. Source data are provided as a Source Data file. Created with BioRender.com.