Fig. 3: FAP derived complement factor C3 is a mediator for monocyte/macrophage interaction.

A Receptor-ligand analysis of mononuclear cells from human skeletal muscle identifies diverse communicative pathways from fibro-adipogenic progenitors (FAPs) to endothelial cells, lymphatic endothelial cells, and monocytes/macrophages. B Communicative pathways from resident mononuclear cells to macrophages shows a large degree of interaction between FAPs and monocytes/macrophages with C3- and MIF-pathways having the highest probability (significant interactions identified by Wilcoxon rank-sum test). C Computed centrality scores heatmap of complement signaling in human skeletal muscle is specific for FAP-monocyte/macrophage communication. D FAP expression of C3 compared to other mononuclear cell populations in human skeletal muscle. E, F FAP ability for C3 production and secretion was confirmed by C3 immunostaining (n = 4, biological replicates) and ELISA (n = 8, biological replicates, one-way ANOVA and Dunnett’s test to correct for multiple comparisons) of C3 in conditioned media from freshly isolated FAPs (CD34⁺CD31^-CD56^-CD45^-) using MuSCs (CD56⁺CD82⁺CD31^-CD34^-CD45^-) and Endothelial cells (CD31⁺CD45^-) as a control populations (n = 8, biological replicates). Scale bar represents 75 µm. G C3 expression was increased in response to injury in spatial transcriptomic data (n = 3, biological replicates). Mono/macro = monocyte/macrophage.