Direct MECOM chromatin network is repressed in primary leukemia cells. (A) UMAP of 64 682 cells generated using scATAC-seq from remissions of patients with pediatric AML (n = 20). Cells were colored by predicted cell type derived using label transfer of matching scRNA-seq data. Labels were derived from Lambo et al.³⁶ (B) UMAP showing the same cohort as panel A and colored by lineage scores. Lineage scores were calculated as the total insertions in 5000 accessible sites in each lineage, normalized to accessible sites in the other 2 lineages (accessible sites derived from Lambo et al³⁶). (C) Cells colored by chromatin accessibility at MECOM-bound loci that were identified to increase in accessibility after the depletion of MECOM. Scores were calculated by ATAC-seq reads at MECOM-bound loci divided by ATAC-seq reads in the TSS and corrected for Tn5 bias. Scores were scaled to the 99th quantile to reduce the effect of outliers. (D) Spearman correlation between lineage scores and MECOM cisRE scores. Each dot represents 1 cell, with cells colored by density. (E) UMAP showing a trajectory inferred using Monocle from inferred HSCs to inferred monocytes. (F) UMAP showing the scaled expression of MECOM in counts from linked scRNA data across cells from remissions. (G) Heat maps showing the scaled expression of MECOM-regulated genes (n = 122) and cisREs (n = 837) along the monocyte trajectory (pseudotime). Each column represents an aggregated minibulk from cells across the inferred pseudotime (100 bins in total). Normalized gene expression scores are derived from linked scRNA samples, with ATAC-seq signal normalized by TSS insertions and Tn5 bias. Both gene expression and ATAC-seq signal were scaled across all cells in the pseudotime. cDC, conventional dendritic cell; CLP, common lymphoid progenitor; GMP, granulocyte-monocyte progenitor; NK, natural killer; pDC, plasmacytoid dendritic cells.