Mitochondrial pyruvate is transiently required by both myeloid progenitors and mature cells. (A) Schematic representation of mixed bone marrow chimeras to assess the hematopoietic requirement for Mpc2 (Mpc2^fl/fl; ROSA26 CreER^−/− or ROSA26 CreER^+/−), both immediately following deletion and after prolonged deletion (10+ wk after tamoxifen). (B) Representative flow cytometry plots of CD45.2 chimerism of Ly6C^hi monocytes and neutrophils for Mpc2 control, recent KO, and prolonged KO chimeras. (C) CD45.2 chimerism of splenic immune lineages at early or prolonged timepoints after deletion of Mpc2. Each symbol represents an individual mouse. Mean values ± SEM are shown. Data are pooled from four independent experiments. *, P < 0.05; ***, P < 0.001; and ****, P < 0.0001 by two-way ANOVA with post-hoc Tukey’s multiple comparisons test. (D) Representative flow cytometry plots of CD45.2 chimerism of GMPs and CMoPs. (E) CD45.2 chimerism of bone marrow progenitors described previously with the addition of CMoPs and CDPs at early or prolonged timepoints after deletion of Mpc2. Data are normalized to HSC CD45.2 chimerism. Each symbol represents an individual mouse. Mean values ± SEM are shown, and data are pooled from three independent experiments. *, P < 0.05; **, P < 0.01; ****, P < 0.0001 by two-way ANOVA with post-hoc Tukey’s multiple comparisons test.