Human embryonic stem cells (hESCs) have the capacity of self-renewal as well as differentiation towards three germ layer derivatives which makes them as a source of therapeutic application. hESCs are tremendously prone to cell death after dissociation into single cells. Therefore, it technically hinders their applications. Our recent study has revealed that hESCs can be prone to ferroptosis which differs from those in earlier explorations reporting that cellular detachment results in a process cited as anoikis. Ferroptosis occurs via increasing intracellular iron. Therefore, this form of programmed cell death is distinct from other cell deaths in terms of biochemistry, morphology, and genetics. Ferroptosis is found by excessive iron which plays an important part role in reactive oxygen species (ROS) generation through the Fenton reaction as a cofactor. Many genes are related to ferroptosis under the control of nuclear factor erythroid 2-related factor 2 (Nrf2) which is a transcription factor regulating the expression of genes to protect cells from oxidative stress. Nrf2 was demonstrated to take a perilous role in the suppression of ferroptosis by regulating the iron, antioxidant defense enzymes, usage, and restoration of glutathione, thioredoxin, and NADPH. Mitochondrial function is another target of Nrf2 to control cell homeostasis through the modulation of ROS production. In this review, we will give a succinct overview of lipid peroxidation and discuss the major players in the ferroptotic cascade. Additionally, we discussed the important role of the Nrf2 signaling pathway in mediating lipid peroxidation and ferroptosis, with a focus on known Nrf2 target genes that inhibit these processes and their possible role in hESCs.
Keywords: Ferroptosis; Human embryonic stem cells; Iron; Nrf2; Pluripotency.
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