Cell Stem Cell
Volume 8, Issue 1, 7 January 2011, Pages 59-71
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Article
Proliferative Neural Stem Cells Have High Endogenous ROS Levels that Regulate Self-Renewal and Neurogenesis in a PI3K/Akt-Dependant Manner

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Summary

The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can also play roles as second messengers, activating normal cellular processes. Here, we investigated ROS function in primary brain-derived neural progenitors. Somewhat surprisingly, we found that proliferative, self-renewing multipotent neural progenitors with the phenotypic characteristics of neural stem cells (NSC) maintained a high ROS status and were highly responsive to ROS stimulation. ROS-mediated enhancements in self-renewal and neurogenesis were dependent on PI3K/Akt signaling. Pharmacological or genetic manipulations that diminished cellular ROS levels also interfered with normal NSC and/or multipotent progenitor function both in vitro and in vivo. This study has identified a redox-mediated regulatory mechanism of NSC function that may have significant implications for brain injury, disease, and repair.

Highlights

► Proliferating neural stem cells have high levels of reactive oxygen species (ROS) ► Neural stem cells require ROS for normal levels of self-renewal and neurogenesis ► The effects of ROS on neural stem cells are dependent on PI3K/Akt/mTOR ► Growth factor signaling in neural stem cells uses ROS-dependent mechanisms

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