Fig. 4: Pro-inflammatory valvular macrophages are markedly increased during hyperlipidemia.

a UMAP plot of 3160 leukocytes, colored by the clusters and mouse models as indicated. Apoe^−/− and Ldlr^−/− mice were fed a WD for 16 weeks. b Average expression map of known cell-type marker genes for each cell cluster. Color represents average expression levels which are scaled by z-transformation and limited to a scale from −2.5 to 2.5. Dot size represents the fraction of cells with the expression value of each marker gene for each cluster. c Absolute cell number (left) and relative proportion (right) of leukocyte subsets from each mouse model. d UMAP plot of expression level of marker genes (gray to blue). e Trajectory component plot of 2677 macrophages colored by the cell states, clusters, and mouse models. f Expression map of top10 significant genes for each cell state. Color represents the expression levels, which are scaled by z-transformation and limited to a minimum scale of −2.5. (purple to yellow). g Correlation of Monocle pseudotime with functional features of macrophages. Pro-inflammatory score represents mean expression of featured genes: Il1b, Tnf, Ccl2, Cxcl10, Cxcl2, H2-Ab1, and Itgax. Anti-inflammatory score represents mean expression of featured genes: Mrc1, Lyve1, Folr2, Cbr2, and Il10. Trend line and the top-right text (r) denote LOESS fit and Pearson’s correlation, respectively (top). Boxplot of macrophage functional features in each cluster (bottom) (n = 159 cells for LEU_C5; 907 for LEU_C1; 973 for LEU_C0; 123 for LEU_C7; 182 for LEU_C4; 333 for LEU_C2). Each box depicts the interquartile range (IQR, the range between the 25th and 75th percentile) and median of each score, whiskers indicate 1.5 times the IQR. One-way ANOVA test p-value. h Cell proportion of functional cell states in macrophages for each mouse model.