Extended Data Fig. 5: Transcriptomic changes at the experimental endpoint in UBA1^mut and UBA^wt cells from VEXAS and WT mice.

a, Percentage of human cells in the BM of hematochimeric mice transplanted with UBA1^mut or UBA1^wt HSPCs and euthanized 4 weeks after transplant (n = 3, 4). Median. b-e, Heatmap as in Fig. 4c showing NES for the GSEA performed within clusters in Fig. 6q comparing: VEXAS and WT mice (b); UBA1^mut male cells from VEXAS mice and UBA1^wt male cells from WT mice (c); UBA1^mut male cells and UBA1^wt female cells from VEXAS mice (d); UBA1^wt male cells and UBA1^wt female cells from WT mice (e). f, Schematic representation of the serial transplantation experiment in the competitive setting. g, Percentage of human hematopoietic cells within total live cells in the BM of mice from secondary recipients in f (n = 2). Median. h, Percentage of UBA1^mut cells across hematopoietic populations in the pooled BM from mice in g (n = 1). i, Schematic representation of the competitive transplantation experiment mixing UBA1^wt HSPCs (labelled with a GFP reporter lentiviral vector) with either UBA1^mut or UBA1^wt HSPCs (labelled with a BFP reporter lentiviral vector). j, Number of colonies derived from sorted GFP+ HSPCs retrieved from VEXAS and WT mice. k, UMAP plot of murine Lin- HSPCs from the BM of mice transplanted with UBA1^mut or UBA1^wt HSPCs. Clusters and associated cell types are indicated by name and colors. l, Heatmap as in Fig. 4c showing NES for the GSEA performed within clusters from j. For all panels: Wilcoxon rank-sum test with Benjamini-Hochberg correction. Panels f,i created with BioRender.com.