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Materials and methods Cell lines and culture conditions Cell lines used in the study: Immortalized conditional Gpx4 −/− mouse embryonic fibroblasts expressing Cre-ERt2 (MEF, male) [33] were previously generated [32] with the CRISPR activation system [77] and a mouse Ms4a15 CRISPR guide (Supplementary Table 5) for overexpression, Calu-1 (gift from Brent Stockwell), HEK293T (fetal, ATCC Cat# CRL-3216), H1975 (female, ATCC Cat# CRL-5908)