Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2094208 | Stem Cell Research | 2013 | 14 Pages |
Embryonic stem cells (ESCs) are hypersensitive to many DNA damaging agents and can rapidly undergo cell death or cell differentiation following exposure. Treatment of mouse ESCs (mESCs) with etoposide (ETO), a topoisomerase II poison, followed by a recovery period resulted in massive cell death with characteristics of a programmed cell death pathway (PCD). While cell death was both caspase- and necroptosis-independent, it was partially dependent on the activity of lysosomal proteases. A role for autophagy in the cell death process was eliminated, suggesting that ETO induces a novel PCD pathway in mESCs. Inhibition of p53 either as a transcription factor by pifithrin α or in its mitochondrial role by pifithrin μ significantly reduced ESC death levels. Finally, EndoG was newly identified as a protease participating in the DNA fragmentation observed during ETO-induced PCD. We coined the term charontosis after Charon, the ferryman of the dead in Greek mythology, to refer to the PCD signaling events induced by ETO in mESCs.
► Mouse embryonic stem cells (mESCs) are hypersensitive to DNA damaging agents. ► Etoposide induces massive cell death in mESCs. ► MESC death is dependent upon cathepsins, p53 and EndoG. ► We coined the term charontosis to describe this novel cell death pathway.