Deregulated Expression of Pparγ and PPARγ Co-activators in Fancd2−/− HSPCs
(A) Real-time qPCR measurement of indicated genes in sorted LSKs 2 weeks after transplantation of LSKs from 8- to 12-week-old Fancd2−/− or Fancd2+/+ mice (n = 4/genotype) into lethally irradiated Boy/J recipient mice (n = 6 mice/group, two independent experiments).
(B) Deregulated Pparγ target genes from previously published Fancd2−/− and Fancd2+/+ SLAM microarray.
(C–E) Real-time qPCR mRNA measurement of indicated genes in Fancd2−/− or Fancd2+/+ LSKs (n = 4/genotype) transduced by shScramble or shPparγ (C), or in presence or absence of 100 nM T0070907 (D) or 1 μM troglitazone (E).
(F) LSKs from 8- to 12-week-old Fancd2−/− or Fancd2+/+ mice (n = 4 mice/genotype) were treated for 48 hr with 1 μM troglitazone, and 2,000 live cells were transplanted into lethally irradiated Boy/J mice along with CD45.1 competitor BM recipient cells. The bar graph depicts the blood chimerism (CD45.2+ cells) of recipient mice 10 weeks after transplantation.
(G) Real-time qPCR measurement in sorted LSKs 2 weeks after transplantation of LSKs from 8- to 12-week-old Fancd2−/− or Fancd2+/+ mice transduced with shScramble or shPparγ into lethally irradiated Boy/J recipient mice (n = 4 mice/group).
(H) LSKs were sorted from 8 to 12 weeks old Fancd2−/− or Fancd2+/+ mice (n = 4 mice/genotype), and 2,000 sorted LSKs (CD45.2) were transplanted into lethally irradiated Boy/J mice along with 2,000 competitor LSKs (CD45.1). Mice were injected intraperitoneally every other day with T0070907 (5 mg/kg) or control vehicle (DMSO) (n = 4 mice/group) during the first 4 weeks after transplantation. The bar graph depicts the blood chimerism (CD45.2+ cells) of recipient mice 16 weeks after transplantation.
WT, wild-type. Values are presented as mean ± SD. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.