The role of oxygen in regulating neural stem cells in development and disease

✍ Scribed by David M. Panchision

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 229 KB
• Volume: 220
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21812

✦ Synopsis

Abstract

Oxygen (O~2~) is a substrate for energy production in the cell and is a rapid regulator of cellular metabolism. Recent studies have also implicated O~2~ and its signal transduction pathways in controlling cell proliferation, fate, and morphogenesis during the development of many tissues, including the nervous system. O~2~ tensions in the intact brain are much lower than in room air, and there is evidence that dynamic control of O~2~ availability may be a component of the in vivo neural stem cell (NSC) niche. At lower O~2~ tensions, hypoxia‐inducible factor 1α (HIF1α) facilitates signal transduction pathways that promote self‐renewal (e.g., Notch) and inhibits pathways that promote NSC differentiation or apoptosis (e.g., bone morphogenetic proteins). Increasing O~2~ tension degrades HIF1α, thus promoting differentiation or apoptosis of NSCs and progenitors. These dynamic changes in O~2~ tension can be mimicked to optimize ex vivo production methods for cell replacement therapies. Conversely, disrupted O~2~ availability may play a critical role in disease states such as stroke or brain tumor progression. Hypoxia during stroke activates precursor proliferation in vivo, while glioblastoma stem cells proliferate maximally in a more hypoxic environment than normal stem cells, which may make them resistant to certain anti‐neoplastic therapies. These findings suggest that O~2~ response is central to the normal architecture and dynamics of NSC regulation and in the etiology and treatment of brain diseases. J. Cell. Physiol. 220: 562–568, 2009. © 2009 Wiley‐Liss, Inc.