Downregulation of Multiple Stress Defense Mechanisms During Differentiation of Human Embryonic Stem Cells
Article first published online: 29 NOV 2007
Copyright © 2008 AlphaMed Press
Volume 26, Issue 2, pages 455–464, February 2008
How to Cite
Saretzki, G., Walter, T., Atkinson, S., Passos, J. F., Bareth, B., Keith, W. N., Stewart, R., Hoare, S., Stojkovic, M., Armstrong, L., von Zglinicki, T. and Lako, M. (2008), Downregulation of Multiple Stress Defense Mechanisms During Differentiation of Human Embryonic Stem Cells. STEM CELLS, 26: 455–464. doi: 10.1634/stemcells.2007-0628
- Issue published online: 2 JAN 2009
- Article first published online: 29 NOV 2007
- Manuscript Accepted: 19 NOV 2007
- Manuscript Received: 3 AUG 2007
- Stem cells;
- Reactive oxygen species;
- DNA damage Disposable soma
Evolutionary theory predicts that cellular maintenance, stress defense, and DNA repair mechanisms should be most active in germ line cells, including embryonic stem cells that can differentiate into germ line cells, whereas it would be energetically unfavorable to keep these up in mortal somatic cells. We tested this hypothesis by examining telomere maintenance, oxidative stress generation, and genes involved in antioxidant defense and DNA repair during spontaneous differentiation of two human embryonic stem cell lines. Telomerase activity was quickly downregulated during differentiation, probably due to deacetylation of histones H3 and H4 at the hTERT promoter and deacetylation of histone H3 at hTR promoter. Telomere length decreased accordingly. Mitochondrial superoxide production and cellular levels of reactive oxygen species increased as result of increased mitochondrial biogenesis. The expression of major antioxidant genes was downregulated despite this increased oxidative stress. DNA damage levels increased during differentiation, whereas expression of genes involved in different types of DNA repair decreased. These results confirm earlier data obtained during mouse embryonic stem cell differentiation and are in accordance with evolutionary predictions.
Disclosure of potential conflicts of interest is found at the end of this article.