Fig. 3: Mouse and human Dnmt3a-mutant HSPCs are sensitive to electron transport chain inhibitors. | Nature Communications

Fig. 3: Mouse and human Dnmt3a-mutant HSPCs are sensitive to electron transport chain inhibitors.

From: Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis

Fig. 3: Mouse and human Dnmt3a-mutant HSPCs are sensitive to electron transport chain inhibitors.

A Quantification of puromycin incorporation in control and Dnmt3aR878H/+ HSCs treated with vehicle control (DMSO), 2-deoxygluocse (2-DG), oligomycin (Oligo) or 2-DG + Oligo using SCENITH assay. Bars represent mean ± SEM with points from biological replicate mice (n = 5 DMSO, n = 5 2-DG, n = 5 Oligo, n = 6 2-DG+Oligo). Statistical analyses used two-way ANOVA with Tukey’s multiple comparisons test. B Quantification of metabolic function in control and Dnmt3aR878H/+ HSCs after treatment with MitoQ using SCENITH assay. Bars represent mean ± SEM with points from biological replicate mice (n = 4 DMSO, n = 7 MitoQ). Statistical analyses used two-way ANOVA with Dunnett’s multiple comparisons test. C Experimental design. D OCR profile plot (left) used to quantify basal and maximal respiration (right) and (E), spare respiratory capacity. D, E Symbols represent mean ± SEM, bars represent mean ± SEM with points from biological replicate mice (n = 4). Statistical analyses used two-way ANOVA with Tukey’s multiple comparisons test (D) and one-way ANOVA with Tukey’s multiple comparisons test (E). F Experimental design. G OCR profile plot (left) used to quantify basal and maximal respiration (right) and (H), spare respiratory capacity. FH Symbols represent mean ± SEM, bars represent mean ± SEM with points from biological replicates (n = 4). Statistical analyses used two-way ANOVA with Tukey’s multiple comparisons test (G) and one-way ANOVA with Fisher’s LSD (H). Source data are provided as a Source Data file.

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