Figure 4. Klf5, Ikzf1, and Stat3 regulate steady-state and inflammatory age-related myeloid bias.

Bone marrow cells from young and aged C57BL/6 mice were transduced with constructs to either knock-down (denoted SH in A-F), or overexpress (denoted OE in G-L) the indicated transcription factors. These cells were subsequently reconstituted into lethally irradiated young C57BL/6 recipient mice. These mice were subsequently challenged with a single sub-lethal dose of LPS and peripheral blood immune cells were tracked over time by flow cytometry. Shown are peripheral blood myeloid cells for mice with knockdown or overexpression of (A,G) Ikzf1, (B,H) Klf5, and (C,I) Stat3. These mice were subsequently harvested and the bone marrow was analyzed for the frequency of (D,J) LT-HSCs, (E,K) CMPs, and (F,L) CLPs from knockdown and overexpression mice, respectively. Data represent at least two independent experiments (n=8–10 mice per group) and are presented as mean ± SEM. (A)-(C) and (G)-(H) ^ denotes p<0.05 for aged shRNA or OE vs. Aged MG, ^vdenotes p<0.05 for aged shRNA or OE vs. young MG using two way ANOVA. (D-F, J-L) * denotes p < 0.05, ** denotes p < 0.01 and *** denotes p < 0.001. P-values was corrected for multiple hypothesis testing by Bonferroni’s method.