Fig. 4: Convergence of dysregulated transcriptional programs in single cells. | Nature Communications

Fig. 4: Convergence of dysregulated transcriptional programs in single cells.

From: Convergence of oncogenic cooperation at single-cell and single-gene levels drives leukemic transformation

Fig. 4

a Expression of marker genes for HSC/MPP, GMP, and granulocytes (GN) along the HSC/MPP-to-myeloid differentiation pseudotime at T3. Heatmap shows normalized gene expression levels. b Scatter plots are shown for the expression of Gcnt2 and Mpo. Each dot represents a single cell. c Increased frequency of cells co-expressing Gcnt2 and Mpo in G12D/E2-KO HSPCs. Left graph shows the frequency of cells co-expressing Gcnt2 and Mpo. Results are mean ± SD of downsampling iterations (N = 1000 cells for 10 iterations). Right graph shows the expression of Gcnt2 and Mpo in cells from different genotypes. Boxes show median of the data and quartiles, and whiskers extend up to 1.5× of the interquartile range. P values were calculated by a two-sided t test. d Volcano plots are shown for bulk RNA-seq. Hmga2 and Flt3 were upregulated in E2-KO and G12D HSPCs, respectively. Both Hmga2 and Flt3 were upregulated in G12D/E2-KO HSPCs. The x-axis shows the log2 fold changes of gene expression and the y-axis shows the negative log10 adjusted P values. e Dot plot shows the expression of Flt3 and Hmga2. The size of the dot indicates the fraction of Flt3 or Hmga2-expressing cells and the color indicates average mRNA levels. f Violin plots for Flt3 and Hmga2 expression. Flt3-expressing HSC/MPP and ProMo cells and Hmga2-expressing HSC/MPP and MEP cells were used. g Increased frequency of Flt3 and Hmga2 co-expressing cells in G12D/E2-KO HSPCs. The graphs were prepared as in panel c. h Experimental scheme to determine the effect of HMGA2 knockdown and/or FLT3 inhibition on colony-forming ability of HSPCs. i Knockdown of HMGA2 was validated by qRT-PCR. Results are mean ± SD (N = 4 independent experiments) and analyzed by a one-way ANOVA. ***P < 0.001; ****P < 0.0001. j Combined HMGA2 depletion and FLT3 inhibition by AC220 led to more significant defects in colony-formation ability than individual treatments in G12D/E2-KO HSPCs. Results are mean ± SD (N = 5 independent experiments) and analyzed by a two-way ANOVA. ***P < 0.001; ****P < 0.0001. Source data are provided as a Source Data file.

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