Fig. 5

scRNA-seq data analysis identifies C1Q⁺ TPP1⁺ macrophages as TAM M2 with an altered p53 signaling in CRC. A UMAP visualization of macrophage subpopulations in normal colon mucosa and tumor tissue of CRC patients. B Trajectory analysis of macrophage subpopulations in CRC. FCN1 trajectory and C1Q trajectory show opposite directions. C, D and E Dot plot for the expression of CD163, KMT5A (SETD8), TP53, CDKN1A, IL6 and CCL2 (MCP-1) genes in the indicated macrophage subpopulations in CRC. The color represents the scaled average expression of the indicated genes in each cell type, and the size represents the proportion of cells expressing the indicated genes. F Dot plot for the enrichment of the indicated signaling pathway-associated genes expressed as normalized enrichment score (NES), in C1Q⁺ TPP1⁺ macrophages in CRC tissue vs normal mucosa. The color represents p-value and the size indicates the number of genes significantly enriched in the indicated pathways. P53 pathway is among the top down-regulated pathways. G Immunofluorescence analysis of TPP1, C1Q, FCN1 and p53^K382me1 in tumor tissue derived from a p53^WT CRC patient. The yellow square indicates the inset shown on the right. Scale bars, 20 µm (left panels). p53^K382me1 positivity percentage of TPP1⁺/C1Q⁺ and FCN1⁺ macrophages, in the indicated compartments of tumor tissue derived from a p53^WT CRC patient as shown in left panels. Data are expressed as mean ± SD of three independent experiments. ns, not significant (right panels). (H, I) Dot plot for the enrichment of the indicated signaling pathway-associated genes expressed as normalized enrichment score (NES), in C1Q⁺ TPP1⁻ macrophages (H) and in FCN1⁺ macrophages (I) in CRC tissue vs normal mucosa. The color represents p-value and the size indicates the number of genes significantly enriched in the indicated pathways. See also Figure S5 and Table S5, Table S6