Figure 6.
Ifnar1 deletion in NHD13 and Flt3ITD/NHD13 mice leads to phenotypic MPP depletion and myeloid progenitor expansion, without compromising repopulating activity. (A-D) MPP2, MPP3/4, pGM, and GMP numbers in P14 bone marrow for the indicated genotypes. n = 5 to 19. (E) CFUs per 1000 sorted MPP3/4s for the indicated genotypes. n = 3 to 7. (F) CD45.2 chimerism in recipients of 300 000 donor bone marrow cells of the indicated genotype competed with 300 000 CD45.1 wild-type bone marrow. n = 13 to 14. (G) Limiting dilution transplants from Flt3ITD/NHD13 bone marrow (on Ifnar1+/− and Ifnar1−/− backgrounds). Multilineage and myeloid engraftment results (reconstitution >1%) are shown. n = 10 to 14 per genotype per dose. There was no significant difference in repopulating activity by extreme limiting dilution analysis. (H) CD45.2 chimerism in recipients of 200 pGM or GMP of the indicated genotype competed with 300 000 CD45.1 wild-type bone marrow. n = 13 to 14. (I-J) Percent of recipients with myeloid or B-cell reconstitution after pGM and GMP transplants. (K) Conventional surface marker phenotypes do not reflect self-renewal capacity or lineage potential in Flt3ITD/NHD13 mice, particularly after Ifnar1 deletion. Phenotypic MPPs and pGMs can self-renew, instead. For all panels, error bars reflect the standard deviation. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 by one-way ANOVA with Holm-Sidak posthoc test. ANOVA, analysis of variance.