Stem cells: balancing resistance and sensitivity to DNA damage.
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.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Julia C
JC
Liu
Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Paul H
PH
Lerou
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: galit@hms.harvard.edu.
Galit
G
Lahav
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000502:physiology / Q000528:radiation effects; D011836:Radiation Tolerance
apoptosis; hESCs; mitochondrial priming; p53