Embryonic stem cells (ESCs) are known to be very sensitive to DNA damage and undergo rapid apoptosis even after low-damage doses. By contrast, adult stem cells show variable sensitivity to damage. Here we describe the multiple pathways that have been proposed to affect the sensitivity of stem cells to damage, including proximity to the apoptotic threshold (mitochondrial priming) and the p53 signaling pathway, through activation of transcription or direct interaction with proapoptotic proteins in the cytoplasm. We also discuss which cellular factors might connect mitochondrial priming with pluripotency and the potential therapeutic advances that can be achieved by better understanding of the molecular mechanisms leading to sensitivity or resistance of embryonic or adult stem cells from different tissues.
Bibliographical noteFunding Information:
The authors thank all members of their laboratories for helpful comments and discussions. J.C.L. was supported by a Molecular Biophysics Training Grant (NIH/NIGMS T32008313) and a National Science Foundation Graduate Research Fellowship. P.H.L. was supported by the Charles H. Hood Foundation and NIH/NICHD HD061981. G.L. was supported by NIH/NIGMS GM083303.
- Mitochondrial priming