Oxygen Tension Regulates Survival and Fate of Mouse Central Nervous System Precursors at Multiple Levels
Article first published online: 7 JUN 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 9, pages 2291–2301, September 2007
How to Cite
Chen, H.-L., Pistollato, F., Hoeppner, D. J., Ni, H.-T., McKay, R. D.G. and Panchision, D. M. (2007), Oxygen Tension Regulates Survival and Fate of Mouse Central Nervous System Precursors at Multiple Levels. STEM CELLS, 25: 2291–2301. doi: 10.1634/stemcells.2006-0609
- Issue published online: 2 JAN 2009
- Article first published online: 7 JUN 2007
- Manuscript Accepted: 30 MAY 2007
- Manuscript Received: 28 SEP 2006
- Neural stem cells;
Despite evidence that oxygen regulates neural precursor fate, the effects of changing oxygen tensions on distinct stages in precursor differentiation are poorly understood. We found that 5% oxygen permitted clonal and long-term expansion of mouse fetal cortical precursors. In contrast, 20% oxygen caused a rapid decrease in hypoxia-inducible factor 1α and nucleophosmin, followed by the induction of p53 and apoptosis of cells. This led to a decrease in overall cell number and particularly a loss of astrocytes and oligodendrocytes. Clonal analysis revealed that apoptosis in 20% oxygen was due to a complete loss of CD133loCD24lo multipotent precursors, a substantial loss of CD133hiCD24lo multipotent precursors, and a failure of remaining CD133hiCD24lo cells to generate glia. In contrast, committed neuronal progenitors were not significantly affected. Switching clones from 5% to 20% oxygen only after mitogen withdrawal led to a decrease in total clone numbers but an even greater decrease in oligodendrocyte-containing clones. During this late exposure to 20% oxygen, bipotent glial (A2B5+) and early (platelet-derived growth factor receptor α) oligodendrocyte progenitors appeared and disappeared more quickly, relative to 5% oxygen, and late stage O4+ oligodendrocyte progenitors never appeared. These results indicate that multipotent cells and oligodendrocyte progenitors are more susceptible to apoptosis at 20% oxygen than committed neuronal progenitors. This has important implications for optimizing ex vivo production methods for cell replacement therapies.
Disclosure of potential conflicts of interest is found at the end of this article.