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The Journal of Neuroscience, March 1, 2002, 22(5):1784-1793
Adult Rodent Neurogenic Regions: The Ventricular Subependyma
Contains Neural Stem Cells, But the Dentate Gyrus Contains Restricted
Progenitors
Raewyn M.
Seaberg and
Derek
van
der Kooy
Department of Anatomy and Cell Biology, University of Toronto,
Toronto M5S 1A8, Canada
Neurogenesis persists in two adult brain regions: the ventricular
subependyma and the subgranular cell layer in the hippocampal dentate
gyrus (DG). Previous work in many laboratories has shown explicitly
that multipotential, self-renewing stem cells in the subependyma are
the source of newly generated migrating neurons that traverse the
rostral migratory stream and incorporate into the olfactory bulb as
interneurons. These stem cells have been specifically isolated from the
subependyma, and their properties of self-renewal and multipotentiality
have been demonstrated in vitro. In contrast, it is a
widely held assumption that the "hippocampal" stem cells that can
be isolated in vitro from adult hippocampus reside in
the neurogenic subgranular layer and represent the source of new
granule cell neurons, but this has never been tested directly. Primary
cell isolates derived from the precise microdissection of adult rodent
neurogenic regions were compared using two very different commonly used
culture methods: a clonal colony-forming (neurosphere) assay and a
monolayer culture system. Importantly, both of these culture methods
generated the same conclusion: stem cells can be isolated from
hippocampus-adjacent regions of subependyma, but the adult DG proper
does not contain a population of resident neural stem cells. Indeed,
although the lateral ventricle and other ventricular subependymal
regions directly adjacent to the hippocampus contain neural stem cells
that exhibit long-term self-renewal and multipotentiality, separate
neuronal and glial progenitors with limited self-renewal capacity are
present in the adult DG, suggesting that neuron-specific progenitors
and not multipotential stem cells are the source of newly generated DG
neurons throughout adulthood.
Key words:
hippocampus; subgranular zone; subependyma; stem cells; progenitor cells; neurospheres
Copyright © 2002 Society for Neuroscience 0270-6474/02/2251784-10$05.00/0
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