Fig 1: The interaction network between FAP+ fibroblasts and SPP1+ macrophages.a Heatmap of top predicated ligands expression across MSCs subtypes of NicheNet which was used to predicate ligands expressed by FAP+ fibroblasts that modulate SPP1+ macrophages (left). Bottom, heatmap of relative receptors expression on different myeloid subtypes. Middle, heatmap of significant ligand-receptor pairs between FAP+ fibroblasts and SPP1+ macrophages. FGFR2+ fibroblasts or ICAM1+ fibroblasts as reference cell types for ligand-receptor analysis. b, c UMAP plots showing the relative expression of RARRES2 in MSCs subtypes (b) and CMKLR1 in myeloid cell subtypes (c). Intensity is shown with z-score normalized expression. d Statistical analysis comparing the chemerin concentration in plasma of healthy donor (n = 17, blue) and CRC patients (n = 20, red). The error bars are presented as the mean ± SEM. e Top-ranked ligands inferred to regulate FAP+ fibroblasts by SPP1+ macrophages according to NicheNet. f Dot plots showing the expression percentage (dot size) and intensity (dot intensity) of top-ranked ligands (e) in each myeloid subtype. g Ligand-receptor pairs showing interaction between SPP1+ macrophages and FAP+ fibroblasts ordered by ligand activity (e). h Heatmap showing regulatory potential of top 20 ranked ligand (e) and the downstream target genes in FAP+ fibroblasts. i Representative KEGG pathways enrichment of the predicted target genes expressed in FAP+ fibroblasts. The statistical analysis was performed by Fisher’s test. j Diagrams showing the network of top 3 active ligands (encoded by TGFB1, IL1A, and IL1B) for target genes belonging to ECM and potential signaling pathways. An unpaired two-sided Student’s t-test was performed in (d), *p < 0.5. UMAP, uniform manifold approximation and projection; MSCs, mesenchymal stromal cells; CRC, colorectal cancer. Source data are provided as Source data Fig. 7b–i and Source data Fig. 7j.rds.