Fig. 4: Phenotypic plasticity of KCs upon occupying mo-mac niche in liver metastasis.

a Bar plot showing the frequency of WPRE⁺ macrophages from different genetic background, and integrated genome viewer plot showing transcripts mapping to the WPRE. b UMAP embedding of N-macs and LMAMs from Ccr2^GFP/GFP mice and control littermates. Feature plots showing the expression of KC-identity genes and SAM genes. c-d Re-clustering of LMAMs extracted from Ccr2^GFP/GFP background and littermate control Ccr2^GFP/WT background; e IF staining and quantification of HA tag⁺ KC-derived LMAMs (Ccr2^GFP/GFP: n = 6 for MC38; n = 5 for E0771; n = 3 for HCC; Ccr2^GFP/WT littermates: n = 6 for MC38; n = 5 for E0771; n = 3 for HCC). f,g Re-clustering of WPRE⁺ N-macs and WPRE⁺ LMAMs from Ccr2^GFP/GFP mice (f), and pseudo time analysis revealing the dynamic gene regulatory programs along of KC trans-differentiation (g). h Heatmap showing the downregulation of KC-identity genes and upregulation of SAM genes in KCs when infiltrating into liver metastasis. i Violin plots showing the expression of selected KC-identity genes and SAM genes in normal liver KCs (WPRE⁺ N-macs), KC-derived LMAMs (WPRE⁺ LMAMs) and mo-macs (WPRE⁺ LMAMs). j,k IF staining and quantification of Clec4f expression (indicated by the nuclear-localized tdT) (j, n = 6 for MC38; n = 6 for E0771; n = 3 for HCC) and Timd4 expression (k, n = 5 for MC38; n = 5 for E0771; n = 3 for HCC). Mean ± s.e.m. shown. Smaller dots are values from individual fields. Outlined circles are mean values taken over multiple fields/sections from the same mouse. P values were calculated by comparing individual animals using two-tailed unpaired (e,k) and paired (j) Mann–Whitney U-test.