Figure 5.

Increased AKT and mTORC1 Activity Underlie the Phenotype of MEK1-Deficient or MEK-Inhibited HSCs

Mouse F/F and cKO HSCs and DMSO or iMEK-treated human HSCs were treated with LY294002 (iPI3K) or rapamycin (RAPA; mTORC1 inhibitor) in LTC.

(A) After 6 weeks, cells were harvested and their ability to form colonies was determined in a 10-day CFU assay in the absence of inhibitors.

(B and C) ROS levels and Δψ per mitochondrial mass (B) and intracellular signaling (C) were also determined and are shown for the HSC and multipotent progenitor (MPP) subset. Data show fold change relative to mouse F/F or human untreated cells (normalized as 1; dotted line; n = 3).

Error bars represent the SD of the mean. ^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001. White asterisks, untreated versus iP3K/RAPA-treated cultures of the same genotype. See also Figures S5 and S6.