Figure 1.
Single-cell chromatin accessibility profiling reveals pAML subtype-specific epigenetic features. (A) Schematic overview of the experimental workflow. Bone marrow mononuclear cells (BMMCs) and CD34+ cells were isolated from patients with pAML including 5 molecular subtypes at diagnosis (n = 28) and healthy donors (HDs; n = 8) and subjected to mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (mtscATAC-seq). (B) Uniform manifold approximation and projection (UMAP) display of chromatin accessibility profiles of 36 586 single cells from HDs (BMMCs, n = 5; CD34+ HSPCs, n = 3). Dots represent individual cells, and colors indicate cluster identity. (C) Projection of disease cells onto the hematopoietic reference map in panel B. Gray dots denote cells from HDs, whereas colored dots represent cluster identities of malignant cells from patients. Bar plot showing the proportion of defined cell types in each patient with pAML. The dotted line highlights cell types significantly enriched in distinct subtypes, with a representative patient displayed for each subtype. (D) UMAP visualization of scATAC-seq data from all pAML samples (n = 28) and healthy individuals (n = 8) at single-cell level, with cells color-coded by molecular subtype. (E) Unsupervised hierarchical clustering of chromatin accessibility profiles across all patients including HD and pAML samples. (F) Heat map illustrating differentially accessible regions (n = 147 028) in each pAML subtype and HDs. The color represents normalized chromatin accessibility. Representative genes relevant to each subtype are displayed. (G) Enriched TF motifs based on differentially accessible regions in pAML. Top 5 motifs for each patient were displayed. Color represents significance of motif enrichment. (H) Footprints of subtype-specific TFs including POU4F3, RUNX2, GATA1, and FOS. Lines are colored by pAML subtypes. CDP, common dendritic cell progenitor; EBM, eosinophil/basophil/mast cell; GMP, granulocyte/macrophage progenitor; LMPP, lymphoid-primed multipotential progenitor; MDP, monocyte-dendritic cell progenitor; MEP, megakaryocyte/erythroid progenitor; MLP, multilymphoid progenitor; NeP, neutrophil progenitor; NK, natural killer cell; Pre-B, precursor B cell; Pro-B, progenitor B cell.

Single-cell chromatin accessibility profiling reveals pAML subtype-specific epigenetic features. (A) Schematic overview of the experimental workflow. Bone marrow mononuclear cells (BMMCs) and CD34+ cells were isolated from patients with pAML including 5 molecular subtypes at diagnosis (n = 28) and healthy donors (HDs; n = 8) and subjected to mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (mtscATAC-seq). (B) Uniform manifold approximation and projection (UMAP) display of chromatin accessibility profiles of 36 586 single cells from HDs (BMMCs, n = 5; CD34+ HSPCs, n = 3). Dots represent individual cells, and colors indicate cluster identity. (C) Projection of disease cells onto the hematopoietic reference map in panel B. Gray dots denote cells from HDs, whereas colored dots represent cluster identities of malignant cells from patients. Bar plot showing the proportion of defined cell types in each patient with pAML. The dotted line highlights cell types significantly enriched in distinct subtypes, with a representative patient displayed for each subtype. (D) UMAP visualization of scATAC-seq data from all pAML samples (n = 28) and healthy individuals (n = 8) at single-cell level, with cells color-coded by molecular subtype. (E) Unsupervised hierarchical clustering of chromatin accessibility profiles across all patients including HD and pAML samples. (F) Heat map illustrating differentially accessible regions (n = 147 028) in each pAML subtype and HDs. The color represents normalized chromatin accessibility. Representative genes relevant to each subtype are displayed. (G) Enriched TF motifs based on differentially accessible regions in pAML. Top 5 motifs for each patient were displayed. Color represents significance of motif enrichment. (H) Footprints of subtype-specific TFs including POU4F3, RUNX2, GATA1, and FOS. Lines are colored by pAML subtypes. CDP, common dendritic cell progenitor; EBM, eosinophil/basophil/mast cell; GMP, granulocyte/macrophage progenitor; LMPP, lymphoid-primed multipotential progenitor; MDP, monocyte-dendritic cell progenitor; MEP, megakaryocyte/erythroid progenitor; MLP, multilymphoid progenitor; NeP, neutrophil progenitor; NK, natural killer cell; Pre-B, precursor B cell; Pro-B, progenitor B cell.

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