Flt3^ITD/NHD13 and Flt3^ITD/Runx1^DELdifferentially reprogram hematopoietic progenitors. (A) Heatmap showing clustering of single cells and marker genes based on ICGS2. Clusters are designated by colors in the top bar and numbers assigned by the ICGS2 algorithm. Reactome pathway analyses for marker genes for clusters 10, 11, and 13 are shown to the right. (B) Uniform Manifold Approximation and Projection (UMAP) plots demonstrating clusters of cells from ICGS2 for the indicated genotypes. The gray background indicates cells not included in the indicated genotype. Cluster colors are identical to the coloring scheme in panel A. (C) Bar graph showing percentages of cells for each genotype that populate clusters 7, 10, 11, and 13. ∗∗∗P < .0001 by χ² test relative to wild-type. The cluster 13 population size was also significantly larger in Flt3^ITD/NHD13 relative to single mutants (P < .0001). Cluster 10 and 11 sizes were significantly larger in Flt3^ITD/Runx1^DEL relative to single mutants (P < .0001). (D) Expression of Irf7, a canonical IFN-1 target, and Pbx3, a canonical NHD13 target, projected onto the UMAP plot. The expression was largely restricted to cluster 13 cells. (E) H3K27ac traces for enhancers that map within 100 kb of marker genes for clusters 10, 11, and 13. ICGS2, Iterative Clustering and Guide Gene Selection version 2.