Common Biochemical Origin for Embryonic Stem Cell Death and Differentiation

Various evidences indicate that differentiation and apoptosisshare common features. We aimed to investigate whethermitochondrial apoptosis and specification employ a commonpathway. Our investigation has shown that mitochondria havenon-energetic role during differentiation and mitochondrial apoptosisexecutioners promote differentiation process withoutbeing involved in cell death. Using split luciferase complementaryassay, we showed that delay in apoptosome complex formationcontributes to mouse embryonic stem cells cardiogenicdifferentiation. Then, we assessed the contribution of apoptosishallmarks to human embryonic stem cells (hESCs) cardiogenicdifferentiation. Our results indicate the involvementof mitochondrial attenuated apoptosis-like pathway as well asreversible mitochondrial outer membrane permeabilization incardiogenic differentiation progression. Moreover, we foundthat upon doxorubicin induction, the well-known apoptosisinducer, hESCs can be specified for differentiation. Additionally,our further investigation showed that low level of Apaf-۱expression during early stages of neural differentiation can beconsidered as a possible regulatory barrier by which differentiatingcells control cell death upon rise in ROS (reactive oxygenspecies) elevation and cytochrome c release from mitochondria.