The protective role of GPX4 in naive ESCs is highlighted by induced ferroptosis resistance through GPX4 expression.

ABSTRACT: Ferroptosis, a form of oxidative cell death mediated by lipid peroxidation, is strictly regulated by glutathione peroxidase 4 (GPX4). Knockout of Gpx4 results in embryonic lethality, highlighting its essential role in development. In vitro, mouse embryonic stem cells (mESCs), which represent the naïve pluripotent state, require β-mercaptoethanol (bME) to prevent cell death, unlike human embryonic stem cells, which represent the primed state. We hypothesized that naïve pluripotency is linked to a heightened susceptibility to ferroptosis due to unique metabolic demands and redox imbalances. In this study, we found that bME deprivation induces ferroptosis in naïve ESCs, as evidenced by lipid peroxidation; ferroptosis, however, is less evident in primed ESCs. Mechanistic analyses revealed that

SUBMITTER: Park S 

PROVIDER: S-EPMC11908625 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature