Fig. 4: The NrasG12D/PtenKO TME displays transcriptomic heterogeneity with mixed pro-tumorigenic and inflammatory signatures. | Nature Communications

Fig. 4: The NrasG12D/PtenKO TME displays transcriptomic heterogeneity with mixed pro-tumorigenic and inflammatory signatures.

From: Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma

Fig. 4

a Uniform Manifold Approximation and Projection (UMAP) representation of CD45+ immune cells from control liver (n = 1 mouse; 7447 cells) and NrasG12D/PtenKO HCC (n = 1 mouse; 4814 cells) (left) with annotated populations identified by scRNA-seq (right, Supplementary Data 7). b K-nearest neighbor (KNN) graph (left) and dotplot (right) depicting the differential abundance of cell types between NrasG12D/PtenKO HCC relative to control. Each dot represents a group of cells clustered in ‘neighborhoods’. Colors represent significant logFC (FDR ≤ 0.05), whereas white is non-significant difference in abundance. Edge thickness represents the number of overlapping cells between neighborhoods. c Violin plots depicting the normalized expression levels of inflammatory and immunosuppressive genes in the indicated immune cell subsets in control liver (n = 1) and NrasG12D/PtenKO HCC (n = 1) (Supplementary Data 8). d UMAP representation of the ‘Monocytic cell’ subset (2616 cells) grouped with cDC1 (115 cells) from (a). e K-nearest neighbor (KNN) graph (left) and dotplot (right) depicting the differential abundance of myeloid cell subsets between NrasG12D/PtenKO HCC and control liver from cells grouped as ‘neighborhoods’ in (d). The colored dots represent significant changes in abundance using a threshold of FDR ≤ 0.05, whereas white is non-significant difference in abundance. Edge thickness represents the number of overlapping cells between neighborhoods. f Violin plots depicting the normalized expression levels of inflammatory and immunosuppressive genes in the indicated myeloid cell subsets in control livers and NrasG12D/PtenKO HCC from the ‘Monocytic cell’ population (Supplementary Data 8). Nhood = neighborhood. Statistical significance was determined by two-sided, Wilcoxon rank sum test with Bonferroni multiple testing correction (c, f).*** FDR ≤ 0.001. Source data are provided as a Source Data file.

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