Extended Data Fig. 8: Polyunsaturated ether lipid nanoparticles increase cellular sensitivity to ferroptosis.
From: Plasticity of ether lipids promotes ferroptosis susceptibility and evasion
a, Schematic of the plasmalogen biosynthesis pathway. Genes marked in red highlight pro-ferroptotic genes identified from the CRISPR screens. b, Strategy used to deliver synthetic phospholipids to OVCAR-8 cells using nanoparticles, and the chemical structures of synthetic phospholipids used. c, Viability curves of OVCAR-8 cells expressing the indicated sgRNAs pre-treated with vehicle (sterilized water) or the specified PE nanoparticles, and then treated with indicated concentrations of ML210 or RSL3 for 72 h. n = 4 biologically independent samples. Veh, vehicle used to package the phospholipids. d, Viability curves of OVCAR-8 cells expressing the indicated sgRNAs pre-treated with vehicle or the specified PC nanoparticles, and then treated with indicated concentrations of ML210 or RSL3 for 72 h. n = 4 biologically independent samples. Veh, vehicle used to package the phospholipids. P value for comparing the relative viabilities of NP5: C18:0-C20:4PC treated cells (blue) with that of NP6: C18 (plasm)-C20:4PC (red): for ML210 = 0.0391 μM, P = 0.00741; for ML210 = 0.0781 μM, P = 0.00095; for ML210 = 0.156 μM, P = 0.00177; for ML210 = 0.3125 μM, P = 0.0101; for RSL3 = 0.0156 μM, P = 0.0000468; for RSL3 = 0.03125 μM, P = 0.00241; for RSL3 = 0.0625 μM, P = 0.00104. Two-tailed Student’s t-test. e, Viability curves of 786-O cells expressing the indicated sgRNAs pre-treated with vehicle or the specified PC nanoparticles, and then treated with ferroptosis inducers. n = 4 biologically independent samples. For viability curves, data are mean ± s.d.
