Figure 6. Apoe overexpression decreases HSPC engraftment potential in male mice.

(A) Schematic of HSPC engraftment experiment. Retroviral vectors MigR1 or MigR1-mApoe were transduced into CD45.2 wild-type E14.5 fetal liver cells. These cells were mixed with CD45.1-bearing competitor WT fetal liver cells at 4:1, and injected into lethally irradiated CD45.1/CD45.2 bearing WT female mice. Mice were monitored for two months and assessed for engraftment of GFP+ CD45.2-bearing cells. (B) Percent engraftment of cells transduced with MigR1 (dashed line) or MigR1-mApoe (solid line) at two, four, and eight weeks post-transplantation. N= 5 for MigR1 and N= 6 for MigR1-mApoe recipient mice; 2-way ANOVA was used to calculate biological significance (C) Proposed model for the genotype and hormone-dependent differences observed in female mice. Expression of DNMT3B7 alters DNA cytosine modifications within the Apoe gene and enhances ApoE protein expression. Whereas there is no further significant increase in ApoE in the male bone marrow microenviroment, within the female hormonal environment, with exposure to estrogen/progesterone, there is an increase in ApoE that is associated with DNMT3B7 expression, which leads to downstream signaling of the IL-3 pathway and reduced growth and differentiation of HSPCs. Male bone marrow is depicted in white rectangular boxes and female bone marrow in light grey boxes.