Fig. 2: Generalized activation of CAFs in the TME.

a The mutual interaction among the main TME components and epithelial cells in different tissue origins. b The interaction between fibroblasts and other TME components. The length of arcs represents the predicted interaction counts. c Violin plot of specific marker genes in cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). Mann–Whitney two-sided test is used to test the significance of gene expression level between CAF and NF categories. ***p < 0.001. d Bubble plot showing the expression of tag genes between CAFs and NFs. e Regulons enriched in each fibroblast cluster detected via SCENIC analysis. f Left: activation trajectory of CAFs, which are divided into three states (CAFState1/2/3). Right: histography of the different CAF components in each CAF state. g Left: epithelial-mesenchymal transition (EMT) score enriched along the evolutionary trajectory of CAFs. Right: comparison of EMT scores among three CAF states, state1: n = 2130, state2: n = 4948, state3: n = 8667. The box is bounded by the first and third quartile with a horizontal line at the median and whiskers extend to the maximum and minimum value. Mann–Whitney two-sided test is used to test the significance of EMT scores among different state categories. ***p < 0.001. h Fluctuation of genes along different states. Source data are provided as a Source Data file.