Fig. 4: Impact of stress stimuli on endothelial cells within the TME.

a UMAP plot of endothelial cells in the TME, grouped by cell subtypes. b Heatmap of the average expression levels of the marker genes used for annotation of endothelial cell subtypes. c Proportion of each endothelial cell subtype in all endothelial cells. Statistical significance was indicated (Fisher’s exact test, **p < 0.01). d Proportion of endothelial cells at different stages of the cell cycle. Statistical significance was indicated (Fisher’s exact test, **p< 0.01). Trajectory analysis of endothelial cells, displayed by pseudotime (e) and cell subtype (f). Cell differentiation direction was indicated with red arrows. g Dot plot of Hallmark pathway signature enrichment score in each subtype of endothelial cells. h Volcano plot of DEGs in endothelial cells in the TME between MS and NC mice. i GO pathway enrichment analysis of DEGs in endothelial cells showing the top 10 pathways (adjusted p < 0.05). j GSEA plot showing representative pathways including the cell cycle and cell proliferation in endothelial cells (MS vs NC). k The signature enrichment score (U score) of representative pathways, including the cell cycle and cell proliferation in endothelial cells (MS vs NC). l. CD31 immunofluorescence staining analysis of tumor tissue sections. m Quantification of the CD31 staining in l (mean ± SEM, n = 5).