Extended Data Fig. 4: Different strengths and natures of VEXAS perturbations of hematopoiesis depending on the type of UBA1 mutation in patients.
From: Mechanisms of hematopoietic clonal dominance in VEXAS syndrome
a, CD34 expression in cells from patients BM. b, Significant positively enriched ‘Hallmark’ MSigDB signatures comparing monocytes from patients with VEXAS syndrome and age-matched controls from the San Raffaele cohort by bulk RNA-seq. Wilcoxon rank-sum test with Benjamini-Hochberg correction. c, Volcano plot showing up- (red) and down- (blue) regulated metabolites in monocytes from patients with VEXAS syndrome and age-matched controls from the San Raffaele cohort. d, Distribution of cells in G1, S or G2/M phases of the cell cycle within differentiated cell clusters and samples in Fig. 5a according to signatures from ref. 87. e, Significant enriched ‘Hallmark’ MSigDB signatures across annotated clusters from the scRNA-seq dataset comparing patients with VEXAS syndrome from either of the two cohorts and age-matched controls. Wilcoxon rank-sum test with Benjamini-Hochberg correction. f, Heatmaps as in Fig. 4c showing NES for the GSEA performed within the differentiated clusters in patients with VEXAS syndrome compared to controls and segregating patients by mutations. Wilcoxon rank-sum test with Benjamini-Hochberg correction. g, Expression of NR4A1 and SOCS3 genes in patients with VEXAS syndrome and controls across HSPC clusters. Wilcoxon rank-sum test with Holm-Bonferroni correction. h, Heatmap showing NES for the GSEA performed using the indicated senescence signatures73,74,75 within the HSPC clusters comparing patients with VEXAS syndrome and controls. Wilcoxon rank-sum test with Benjamini-Hochberg correction.
