Single-cell analysis of SETBP1^LSL and SETBP1^G870S BM cells. (A) Left: UMAP projection of the full, integrated SETBP1^G870S/SETBP1^LSL single-cell analysis, annotated with cell type. The orange area highlights the HSC, CMP, GMP, and MEP cell populations. Right: UMAP projection of the HSC, CMP, GMP, and MEP cell populations. The gray line represents the pseudotime path. (B) Gene expression heat map of autocorrelated genes from root to fate in the CMP to MEP (upper panel) and CMP to GMP (lower panel) trajectories for SETBP1^LSL (left) and SETBP1^G870S (right) cells. (C) UMAP plots reporting the expression level of a subset of differentially expressed and autocorrelated genes in a blue-to-yellow color scale. Orange dots identify genes that are differentially expressed in SETBP1^G870S vs SETBP1^LSL; blue and green dots highlight genes that are spatially autocorrelated in the CMP-MEP and CMP-GMP trajectories, respectively; red dots identify genes that represent direct transcriptional SETBP1 targets. (D) Alignment plots of Hoxa9/10, Mecom, Mef2c, and Zbtb20 loci for anti-SETBP1 Cut&Run experiments performed in Lin⁻ BM cells of SETBP1^G870S and SETBP1^LSL mice models. (E) Cumulative distribution of SETBP1 and V5 binding loci relative to transcription start site (TSS). (F) Heat map of anti-SETBP1 Cut&Run reads binding to TSS. (G) Venn diagram showing the intersection between differentially expressed genes (DEGs) identified in SETBP1^G870S vs SETBP1^LSL in CMP, GMP, and MEP clusters, spatially autocorrelated genes in CMP-MEP and CMP-GMP trajectories, and peaks identified in Cut&Run experiments using an anti-SETBP1 antibody. (H) Biological process overrepresentation analysis performed using the intersection of DEGs identified in SETBP1^G870S vs SETBP1^LSL in CMP, GMP, and MEP clusters, spatially autocorrelated genes in CMP-MEP and CMP-GMP trajectories, and peaks identified in Cut&Run experiments as input. The FDR is reported in a blue-to-red color scale.