Fig. 6

PMC_2 interacts strongly with fibroblasts and macrophages within PMC_P. a, b Circle plot (based on pan-tissue scRNA-seq across regions) displaying the intercellular communication between different cell types for AREG \(\longrightarrow\) EGFR/ERBB2, and NAMPT \(\longrightarrow\) ITGA5/ITGB1. c Spearman correlation (region-specific analysis-PMC_P only) between AREG expression and gene signature scores for enterocytes (FABP1, FABP2, and APOA1), PMC_2 (CEACAM5, ITGA2, PHLDA1, ANXA1, DUSP5, and FERMT1), NKT cells (CD160, KRT81, and KIR2DL4), mast cells (TPSB2, MS4A2, TPSAB1, and KIT), and myeloid cells (S100A8, S100A9, IL1B, and CD68) (left), NAMPT expression and gene signature scores for PMC_2 (CEACAM5, ITGA2, PHLDA1, ANXA1, DUSP5, and FERMT1), neutrophil (FCGR3B, CXCR2, IFITM2, CMTM2, and CSF3R), mDC (PPP1R14A, FCER1A, HLA-DPB1, and CD1C), CD14 mono (GIMAP7, AHNAK, and CD36), monocyte (CCDC88C, and POU2F2), M2 macrophage (SLCO2B1, C1QC, C1QA, GPNMB, and C1QB), and VEGFA + M1 (TGM2, CLEC5A, VEGFA, and MCEMP1) (right). d mIHC staining shows ligand-receptor pair NAMPT (secreted by PMC_2 marked by CK + ITGA2+) \(\longrightarrow\) ITGA5/ITGB1 (expressed by fibroblasts marked by DCN) across four regions: N, IM, PMC_P, T. The magnified view within the boxed region highlights NAMPT + PMC_2 cells (white arrows) and ITGB1 + ITGA5+fibroblast cells (red arrows). Scale bar: 50 μm. e mIHC staining illustrates ligand-receptor pair AREG (expressed by macrophages marked by S100A8) \(\longrightarrow\) EGFR/ERBB2 (expressed by PMC_2 marked by CK, and ITGA2) across four regions: N, IM, PMC_P, T. The magnified view within the boxed region highlights EGFR + ERBB2 + PMC_2 cells (white arrows) and AREG+ macrophages (red arrows). Scale bar: 50 μm. f Line charts showing the proportion of AREG+ cells, EGFR + ERBB2 + PMC_2 cells, ITGA5 + ITGB1+ fibroblasts, NAMPT + PMC_2 cells across four regions: N, IM, PMC_P, T. g Distribution of four myeloid cell subtypes showing macrophage as main myeloid cell type in PMC_P region. h Spearman correlation between AREG and myeloid subclusters: mDC (PPP1R14A, FCER1A, HLA-DPB1, and CD1C), CD14 mono (GIMAP7, AHNAK, and CD36), M2 macrophage (SLCO2B1, C1QC, C1QA, GPNMB, and C1QB), and VEGFA + M1 (TGM2, CLEC5A, VEGFA, and MCEMP1). i Spatial distribution of three histological status (i.e., N, IM, and T), spatial clusters by stMVC (N, IM, PMC_P, and T), distributions of five cell types, and zoomed-in views of the cell type distributions from PMC_P to T