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Downregulation of multiple stress defense mechanisms during differentiation of human embryonic stem cells

Lookup NU author(s): Dr Gabriele Saretzki, Theresia Walter, Dr Joao Passos, Dr Rebecca Stewart, Dr Simon Hoare, Professor Miodrag Stojkovic, Professor Lyle Armstrong, Professor Thomas von Zglinicki, Professor Majlinda Lako

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Abstract

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. ©AlphaMed Press.


Publication metadata

Author(s): Saretzki G, Walter T, Atkinson S, Passos JF, Bareth B, Keith WN, Stewart R, Hoare S, Stojkovic M, Armstrong L, Von Zglinicki T, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2008

Volume: 26

Issue: 2

Pages: 455-464

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.

URL: http://dx.doi.org/10.1634/stemcells.2007-0628

DOI: 10.1634/stemcells.2007-0628

PubMed id: 18055443


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