Cell Stem Cell
Volume 6, Issue 5, 7 May 2010, Pages 445-456
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Article
Quiescent and Active Hippocampal Neural Stem Cells with Distinct Morphologies Respond Selectively to Physiological and Pathological Stimuli and Aging

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Summary

New neurons are generated in the adult hippocampus throughout life by neural stem/progenitor cells (NSCs), and neurogenesis is a plastic process responsive to external stimuli. We show that canonical Notch signaling through RBP-J is required for hippocampal neurogenesis. Notch signaling distinguishes morphologically distinct Sox2+ NSCs, and within these pools subpopulations can shuttle between mitotically active or quiescent. Radial and horizontal NSCs respond selectively to neurogenic stimuli. Physical exercise activates the quiescent radial population whereas epileptic seizures induce expansion of the horizontal NSC pool. Surprisingly, reduced neurogenesis correlates with a loss of active horizontal NSCs in aged mice rather than a total loss of stem cells, and the transition to a quiescent state is reversible to rejuvenate neurogenesis in the brain. The discovery of multiple NSC populations with Notch dependence but selective responses to stimuli and reversible quiescence has important implications for the mechanisms of adaptive learning and also for regenerative therapy.

Highlights

► Notch signaling defines morphologically distinct hippocampal stem cell populations ► Radial and horizontal hippocampal stem cells depend on canonical Notch signaling ► Different neural stem cell subpopulations respond selectively to neurogenic stimuli ► Aging results in a reversible transition of stem cells to a quiescent state

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These authors contributed equally to this work