Figure 5

Functional signaling molecules being present in all groups exhibit different patterns of signaling interactions during HCC progression. (A) Heatmaps portraying only selected immunologically relevant signaling and regulatory molecules identified by CellChat with analysis parameters adjusted to use a truncated mean of 2.5%, in order to detect functional signaling pathways in reduced numbers of adaptive immune cells during a WD. (B) Chord diagrams showing the directionality of functional cytokine signaling targeting hepatocytes (TGF-β, IL-1, TNF-α, and FASL), as well as structural cells, and immune cells. (C) Functional patterns of the TNF-α signaling pathway were quantified by assessing the number of cells in each detected cell type involved in the pathway that were TNF-α + (Tnf > 0), TNF-α + /ADAM17 + (double positive and sTNF-α; Tnf > 0 & Adam17 > 0), TNFR1 + (Tnfrsf1a > 0), TNFR2 + (Tnfrsf1b > 0), and TNFR1 + /2 + (double positive; Tnfrsf1a > 0 & Tnfrsf1b > 0); all cells expressing genes are presented as a percentage of the cell type population in each sample. (D) Chord diagrams using CellChat for evaluating unique ligand-receptor in the Ctrl (IL-6 and GITRL), Pre-T (OSM, IL-4, and IFN-γ), and Post-T (RANKL). Figures (A), (B), and (D) were made through the use of CellChat version 1.5.0, and heatmaps in A used the dependent software ComplexHeatmap version 2.15.1 (https://github.com/jokergoo/ComplexHeatmap), while the chord diagrams in (B) and (D) used the dependent software circlize version 0.4.16 (https://github.com/jokergoo/circlize).