UCSF

Neural stem cells (NSCs) generate the diverse types cell types that make up adult brain. NSCs persist in the subventricular zone (SVZ) of the adult rodent brain, where they generate astrocytes, oligodendrocytes, and multiple types of olfactory bulb (OB) neurons. They have astrocyte-like characteristics and act as stem cells in culture, but little is known about their origin or potential in vivo. In this work, I describe a technique to specifically and permanently label radial glial cells in the neonatal mouse brain and demonstrate that as a population, these cells act as multipotent NSCs. Labeled radial glia generate adult NSCs that are neurogenic in vivo and that individual radial glia and their adult SVZ progeny act as multipotent stem cells in vitro. Therefore, throughout development, neural stem cells have glial characteristics. Second, I show that the adult NSCs is a unique cell type that shares features of radial glia and differentiated astrocytes. Third, I show that NSCs persist in the dorsal wall of the lateral ventricle (LV), the anterior medial wall of LV, and in the rostral migratory stream (RMS). Thus, adult neurogenesis occurs in a significantly larger region than has been appreciated. Fourth, I show that NSCs labeled in different neurogenic subregions produce different types of olfactory bulb neurons. Thus, adult NSCs consist of different populations of restricted progenitors segregated into different domains. Finally, I show that the neurogenic potential of these progenitors is maintained during postnatal development and after being cultured or heterotopically grafted, suggesting that adult NSC potential is established during embryonic development and maintained by a cell-autonomous mechanism. Together, these findings suggest that embryonic NSCs transform into adult NSCs that maintain embryonic characteristics and regional identity, but are restricted in their neurogenic potential.