Adult Rodent Neurogenic Regions: The Ventricular Subependyma Contains Neural Stem Cells, But the Dentate Gyrus Contains Restricted Progenitors

Abstract

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 neuronspecific progenitors and not multipotential stem cells are the source of newly generated DG neurons throughout adulthood.

Fluoxetine targets early progenitor cells in the adult brain

“…This characteristic apical process is easily visualized with antibodies to GFAP, nestin, vimentin, and brain fatty acid-binding protein. Cells of this class have been described in detail (13,(17)(18)(19)(20)(21), and they correspond to the most primitive, stem-like population in the DG; note, however, that not all of the criteria of stem cells, e.g., ability to self-renew, have been demonstrated for these cells (22)(23)(24). Only a small fraction of these cells (Ͻ2%) can be labeled by BrdU after a short (2-h) pulse, indicating their low rate of division and consistency with the quiescent state of these cells (18,20); we therefore designate these cells as quiescent neural progenitors (QNP).…”

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…However, there are contrary reports on the location, origin, and potency of these potential stem cells. While the SGZ in the dentate gyrus has been characterized as a niche in vitro (Seaberg and van der Kooy, 2002;Becq et al, 2005;Bull and Bartlett, 2005) and in vivo (Nakatomi et al, 2002), these studies suggest that the CA1 region contains multipotent stem cells while the SGZ contains only precursors. Second, there is evidence for neural stem cell populations in the embryonic and adult cerebellum (Laywell et al, 2000;Klein et al, 2005) and between the hippocampus and corpus callosum in the subcollosal zone (SCZ) (Seri et al, 2006), although the composition of these potential niches is unknown.…”

The Predominant Neural Stem Cell Isolated from Postnatal and Adult Forebrain But Not Early Embryonic Forebrain Expresses GFAP

“…A simple explanation compatible with the present data and those of others is that GFAP is merely one of several intermediate filaments, including nestin and vimentin, that are regulated dynamically and differentially in NSCs during different stages of maturation. Although one interpretation of the expression of GFAP by postnatal and adult NSCs could be that these cells are differentiated astrocytes, adult CNS tissue that contains many astrocytes but is distant from GZ does not exhibit NSC potential under standard conditions in vitro (Reynolds and Weiss, 1992;Morshead et al, 1994;Laywell et al, 2000;Seaberg and van der Kooy, 2002). The relationship between GFAP-expressing NSCs, GFAP-expressing astrocytes, and GFAP-expressing radial glia (see below) requires additional study, and it will be of interest to determine whether differentiated astrocytes have the potential to undergo reprogramming into NSCs or neural progenitors if stimulated appropriately (Kondo and Raff, 2000).…”