Fig. 4. α-Toc rescues HSPCs from ferroptosis ex vivo.
a Schematic illustration of the ferroptosis pathway and the targets of different drugs. Ferroptosis was triggered by iron-dependent accumulation of lipid peroxidation. GPX4 makes use of GSH to reduce lipid peroxidation and inhibit ferroptosis. Ferroptosis can be induced by the GPX4 inhibitor RSL3 and inhibited by the iron chelator DFO or lipophilic antioxidants such as Fer-1 and α-Toc. N-Acetyl-L-cysteine (NAC) is the precursor of cysteine, which promotes GSH synthesis. LSK cells (b, c) or GMPs (d, e) from the Gpx4flox/flox Vav-Cre mice were cultured with NAC or α-Toc. The viability and lipid ROS levels of these cells were measured (n = 3 mice). f LT-HSCs derived from the Gpx4flox/flox Vav-Cre mice were tested with single-cell colony-forming assay in a medium containing NAC or α-Toc (n = 3 mice). # indicates no colony was formed. Data are the mean ± SD. (ns not significant, ***P < 0.001).