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. 2019 Sep 16;47(21):e138. doi: 10.1093/nar/gkz789

Figure 4.

Figure 4.

Cell population-specific impacts in transitioning progenitors and AML. (A) cellHarmony alignment of previously profiled splenic c-kit-positive AML cells relative to ICGS results from all captured normal mouse bone marrow hematopoietic progenitors (reference sample, Olsson et al. 2016). (B) AML cells were aligned most frequently to annotated dendritic cells (DC), monocyte progenitors (Mono), and previously described bipotential hematopoietic progenitors (IG2, Olsson et al. 2016). The AML DCs were high enriched relative to wild-type DCs by cellHarmony Fisher Exact test (P = 4.8E–24). C) Number of differentially expressed genes (DEG) by cell cluster (upregulated and down-regulated) for AML versus wild-type cell populations (fold > 2, P < 0.05, FDR adjusted). Negative numbers on the x-axis indicate downregulation (i.e. ‘-100’ means ‘100 downregulated genes’). (D) Heatmap of AML versus wild-type fold changes for all significant differentially regulated genes from panel C. Genes are grouped as global, regional, and local transcriptomic differences (DEG p-value ranked), with DEGs demonstrating global regulation shown at the top of the heatmap, co-regulated cluster impacts in the middle, and cell population-specific impacts at the bottom. The regional or co-regulated clusters indicate shared patterns of gene expression across multiple cell populations (e.g. HSCP-1 + HSCP-2 + IG2 + Mono). For each pattern, a separate up-regulated and down-regulated cluster is shown. Known transcription factors are displayed to the right of the heatmap where present by cellHarmony and enriched Pathway Commons gene-sets (blue) and transcription factor target sets (red) are displayed on the left next to each cluster in ranked order of significance (bottom to top). (E) Corresponding gene expression differences from bulk RNA-Seq of the AML model compared to wild-type bone marrow controls as an independent verification. Red lines = upregulated genes (fold >1.5, empirical Bayes moderated t-test P < 0.05 (FDR adjusted)), Blue lines = downregulated genes (fold < –1.5, empirical Bayes moderated t-test P < 0.05 (FDR adjusted)).