Fig. 6: Identification of new candidate regulators of leukemia-initiating cells. | Nature Communications

Fig. 6: Identification of new candidate regulators of leukemia-initiating cells.

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

Fig. 6

a Identification of genes highly expressed in HSC/MPP and synergistically activated in G12D/E2-KO HSPCs (red dots). Each dot represents a single gene. The x-axis depicts the log-transformed expression fold changes between G12D/E-KO and WT HSC/MPP. The y-axis depicts the correlation to HSC/MPP prediction scores. b Violin plot is shown for Gem expression in HSC/MPP from different genotypes. c The interaction scores of G12D and E2-KO on Gem expression at different time points. d GEM expression is upregulated in human AML cells relative to control HSPCs in the Beat AML cohorts. Each dot indicates an independent sample (N = 19 and 451 for healthy and AML samples). Boxes show the median of the data and quartiles (log2 RPKM), and whiskers extend to 1.5× of the interquartile range. P values were calculated by a two-sided t-test. e Increased GEM expression is associated with adverse ELN risk groups in AML. Boxes show the median of the data and quartiles (log2 RPKM), and whiskers extend to 1.5× of the interquartile range. P values were calculated by a two-sided t test (N = 19, 117, 150, and 162 for healthy, favorable, intermediate, and adverse samples, respectively). f Increased GEM expression associated with poor survival in AML. AML patients were ranked by GEM mRNA levels and divided into GEM-low (bottom 50%) and GEM-high (top 50%) groups. P values were calculated using the log-rank (Mantel–Cox) test. g Gem expression is shown on the UMAP graph of the indicated genotypes at T3. Each dot represents a single cell. Color scale shows Gem expression level. h Browser view of Gem locus with H3K27ac, H3K4me1, and ETS1 ChIP-seq in MEL cells. Candidate Gem enhancers (E1, E2, and E3) and neighboring control regions (C1–C3) are indicated. i ETS1 associates with candidate Gem enhancers in HSPCs. Results are mean ± SD and analyzed by two-way ANOVA. j, ETS1 depletion impairs Gem expression in G12D/E2-KO HSPCs. Results are mean ± SD and analyzed by one-way ANOVA. Source data are provided as a Source Data file.

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