Extended Data Fig. 6: Mutant ASXL1-derived monocytes/macrophages show inflammatory-biased features.

a: Bar graph of the cell counts of each cluster in scRNA-seq analysis of plaque cells. UMAP plot of CD45+ cells from aortas of Ldlr−/− mice with 100% bone marrow of the indicated genotypes (1st experiment: control 1 mouse, ASXL1-MT 1 mouse; 2nd experiment: control 2 mice pooled; ASXL1-MT 2 mice pooled). Data are the mean ± s.d.; Data were analysed by Two-way ANOVA and Šídák’s multiple comparisons test. Column (mutation) Factor; P = 0.0094. Šídák’s multiple comparisons test; P = 0.0341 (Res-like macrophages), P = 0.0415 (Granulocytes-1). b: Violin plots of Cxcl12 in Cluster 2 Res-like macrophages. c: Feature plots of the 1st experimental pair merged with Cxcr4 (red) and Cxcl12 (green). d: Dot plots of the gene set enrichment analysis (GSEA) of inflammatory macrophages (Cluster 0 and 4) and of monocytes (Cluster 10) from aorta of Ldlr–/– mice. The significance test is single tail test on the appropriate (positive/negative) side of the null distribution. e, f: Bulk RNA-seq data of plaque CD11b+ F4/80+ macrophages from mice transplanted with ASXL1-MT BMCs or mice transplanted with control BMCs (n = 3 per group). Relative mRNA expression (FPKM) of regulatory genes for Toll-like receptor (TLR)/IL-1 receptor signalling (e) and of inflammasome/Map3k genes (f) in aortic macrophages derived from ASXL1-MT-KI bone marrow versus control. Data are shown as the mean ± s.d.; Unpaired t-tests (e, f).