0000000000557581
AUTHOR
Isabelle Caillé
Multipotent Neural Stem Cells Reside into the Rostral Extension and Olfactory Bulb of Adult Rodents
The lateral walls of the forebrain lateral ventricles are the richest source of stem cells in the adult mammalian brain. These stem cells give rise to new olfactory neurons that are renewed throughout life. The neurons originate in the subventricular zone (SVZ), migrate within the rostral extension (RE) of the SVZ along the rostral migratory stream (RMS) within tube-like structures formed of glial cells, to eventually reach the olfactory bulb (OB). We demonstrate that, contrary to the current view, multipotential (neuronal-astroglial-oligodendroglial) precursors with stem cell features can be isolated not only from the SVZ but also from the entire RE, including the distal portion within the…
EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells.
AbstractNeural stem cells in the subventricular zone (SVZ) continue to generate new neurons in the adult brain. SVZ cells exposed to EGF in culture grow to form neurospheres that are multipotent and self-renewing. We show here that the majority of these EGF-responsive cells are not derived from relatively quiescent stem cells in vivo, but from the highly mitotic, Dlx2+, transit-amplifying C cells. When exposed to EGF, C cells downregulate Dlx2, arrest neuronal production, and become highly proliferative and invasive. Killing Dlx2+ cells dramatically reduces the in vivo response to EGF and neurosphere formation in vitro. Furthermore, purified C cells are 53-fold enriched for neurosphere gene…
Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain
AbstractNeural stem cells reside in the subventricular zone (SVZ) of the adult mammalian brain. This germinal region, which continually generates new neurons destined for the olfactory bulb, is composed of four cell types: migrating neuroblasts, immature precursors, astrocytes, and ependymal cells. Here we show that SVZ astrocytes, and not ependymal cells, remain labeled with proliferation markers after long survivals in adult mice. After elimination of immature precursors and neuroblasts by an antimitotic treatment, SVZ astrocytes divide to generate immature precursors and neuroblasts. Furthermore, in untreated mice, SVZ astrocytes specifically infected with a retrovirus give rise to new n…
Lack of the Cell-Cycle Inhibitor p27Kip1 Results in Selective Increase of Transit-Amplifying Cells for Adult Neurogenesis
The subventricular zone (SVZ) is the largest germinal layer in the adult mammalian brain and comprises stem cells, transit-amplifying progenitors, and committed neuroblasts. Although the SVZ contains the highest concentration of dividing cells in the adult brain, the intracellular mechanisms controlling their proliferation have not been elucidated. We show here that loss of the cyclin-dependent kinase inhibitor p27Kip1 has very specific effects on a population of CNS progenitors responsible for adult neurogenesis. Using bromodeoxyuridine and [3H]thymidine incorporation to label cells in S phase and cell-specific markers and electron microscopy to identify distinct cell types, we compared th…