Figure 3.

Inhibition of PPARγ Activity Improves HSC Self-Renewal and BM Repopulation Capacity

(A and B) CFU assay with LSK cells after shRNA knockdown (A) or treatment with the PPARγ agonist (troglitazone) or antagonist (T0070907) (B).

(C) LSKs isolated from Fancd2^+/+ or Fancd2^−/− mice (n = 5 donors/group, two independent experiments) were transduced with shRNA targeting Pparγ or scrambled shRNA control. The transduction efficiency was 25%–33% before transplantation and was normalized to 1. Transduced cells, along with untransduced cells, were transplanted into lethally irradiated Boy/J (n = 8 mice/group, two independent experiments). The graph shows relative changes in GFP⁺ proportion among donor-derived Lin⁻ BM cells (CD45.2) at 16 weeks after transplantation.

(D–F) Transduced GFP⁺ LSKs were sorted and transplanted into lethally irradiated Boy/J recipient mice. (D) Representative plot and histograms depict the LSK (Lin⁻Sca1⁺cKit⁺) and SLAM (CD48⁻CD150⁺LSKs) percentage among GFP⁺ mononuclear donor-derived cells (CD45.2) at 16 weeks after transplantation. (E) Absolute number of BM MNC, LSKs, and SLAM cells at 16 weeks after sorted LSK transplantation. (F) Lymphocytes (Cd3e), B cells (B220), and granulocytes (Gr1Mac1) population percentage into CD45⁺ cells from the blood of 16-week transplanted mice.

WT, wild-type. Values are presented as mean ± SD. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.