Extended Data Fig. 3: VEXAS-causing UBA1 mutation induces pan-lineage perturbation of hematopoietic cell states.

a, Number of human CD45+ cells homed to the BM 3 days after transplantation of UBA1^wt or UBA1^mut HSPCs (n = 3). Median. b, Percentage of cells within human CD45+ cells in spleen (left) and BM (right) of mice from Fig. 3j (n = 4/group). Mean ± s.e.m. c, Erythroid (left), B-cell (middle), and myeloid (right) pseudotime trajectories starting from the HSC/MPP cluster in UMAP plot (top) and distribution of cells along the trajectory (bottom) from Fig. 4e. d, Significant positively (red) and negatively (blue) enriched ‘Hallmark’ MSigDB signatures comparing GMP-2 versus GMP-1 clusters from Fig. 4e. Wilcoxon rank-sum test with Benjamini-Hochberg correction. e, Projection of CD34+ HSPCs from 100% UBA1^wt and 40% UBA1^mut scRNA-seq on a BM reference map⁶⁹. f, Cell abundance in the indicated clusters from ‘e’. g-i, AUcell scores of selected ‘Hallmark’ MSigDB database signatures (g,h) and aged HSC signatures from^71,72 (i) within primitive HSCs/MPPs according to projection on the BM reference map in ‘e’. Wilcoxon rank-sum test with Benjamini-Hochberg correction. j, Heatmap showing normalized enrichment scores (NES) for the GSEA performed using the indicated senescence signatures^73,74,75 within the HSPC clusters from Fig. 4e. Wilcoxon rank-sum test with Benjamini-Hochberg correction.