Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke (original) (raw)
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Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System
Cell, 1999
and Molecular Biology stem cell has previously been suggested to reside in the subventricular zone (Lois and Alvarez-Buylla, 1993; † Medical Nobel Institute ‡ Department of Neuroscience Morshead et al., 1994). However, there are reasons to believe that the subventricular zone instead harbors the Karolinska Institute S-171 77 Stockholm transit amplifying progenitor cell. First, depletion of the rapidly proliferating cell population does not affect Sweden the number of stem cells that can be isolated from the brain (Morshead et al., 1994). Second, it is possible to isolate stem cells from all regions of the nervous system Summary containing extensions of the ventricular system, including the spinal cord (Weiss et al., 1996), which does not New neurons are continuously added in specific recontain a subventricular zone. gions of the adult mammalian central nervous system. Assuming that the subventricular zone is the site of These neurons are derived from multipotent stem cells the transit amplifying progenitor cells, it leaves open the whose identity has been enigmatic. In this work, we possibility that the cells in the ependymal layer are the present evidence that ependymal cells are neural stem adult neural stem cells. This may appear counterintuitive cells. Ependymal cells give rise to a rapidly proliferatgiven that ependymal cells are thought not to proliferate ing cell type that generates neurons that migrate to in the adult animal and to play a critical role as a barrier the olfactory bulb. In response to spinal cord injury, between the cerebrospinal fluid and the neural tissue ependymal cell proliferation increases dramatically to (Del Bigio, 1995). During embryogenesis, however, neugenerate migratory cells that differentiate to astroral stem cells in the ventricular zone line the lumen of cytes and participate in scar formation. These data the neural tube, corresponding to the localization of demonstrate that ependymal cells are neural stem ependymal cells in the adult animal. In addition, nestin, cells and identify a novel process in the response to a protein expressed by neural stem cells (Lendahl et al., central nervous system injury. 1990), is most highly expressed in ependymal cells and at lower levels in the rapidly proliferating subventricular zone progenitor cells in adult mammals (Doetsch et al.,
The Journal of Comparative Neurology, 2005
The lateral wall of the lateral ventricle in the human brain contains neural stem cells throughout adult life. We conducted a cytoarchitectural and ultrastructural study in complete postmortem brains (n ϭ 7) and in postmortem (n ϭ 42) and intraoperative tissue (n ϭ 43) samples of the lateral walls of the human lateral ventricles. With varying thickness and cell densities, four layers were observed throughout the lateral ventricular wall: a monolayer of ependymal cells (Layer I), a hypocellular gap (Layer II), a ribbon of cells (Layer III) composed of astrocytes, and a transitional zone (Layer IV) into the brain parenchyma. Unlike rodents and nonhuman primates, adult human glial fibrillary acidic protein (GFAP)ϩ subventricular zone (SVZ) astrocytes are separated from the ependyma by the hypocellular gap. Some astrocytes as well as a few GFAP-cells in Layer II in the SVZ of the anterior horn and the body of the lateral ventricle appear to proliferate based on proliferating cell nuclear antigen (PCNA) and Ki67 staining. However, compared to rodents, the adult human SVZ appears to be devoid of chain migration or large numbers of newly formed young neurons. It was only in the anterior SVZ that we found examples of elongated Tuj1ϩ cells with migratory morphology. We provide ultrastructural criteria to identify the different cells types in the human SVZ including three distinct types of astrocytes and a group of displaced ependymal cells between Layers II and III. Ultrastructural analysis of this layer revealed a remarkable network of astrocytic and ependymal processes. This work provides a basic description of the organization of the adult human SVZ. J.
Cell and Tissue Research, 2015
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Characterization of the ventricular-subventricular stem cell niche during human brain development
Development (Cambridge, England), 2018
Human brain development proceeds via a sequentially transforming stem cell population in the ventricular-subventricular zone (V-SVZ). An essential, but understudied, contributor to V-SVZ stem cell niche health is the multi-ciliated ependymal epithelium, which replaces stem cells at the ventricular surface during development. However, reorganization of the V-SVZ stem cell niche and its relationship to ependymogenesis has not been characterized in the human brain. Based on comprehensive comparative spatiotemporal analyses of cytoarchitectural changes along the mouse and human ventricle surface, we uncovered a distinctive stem cell retention pattern in humans as ependymal cells populate the ventricle surface in an occipital-to-frontal wave. During perinatal development ventricle-contacting stem cells are reduced. By 7-months few stem cells are detected, paralleling neurogenesis decline. In adolescence and adulthood, stem cells and neurogenesis are not observed along the lateral wall. V...
Neuron, 1994
Dissection of the subependyma from the lateral ventricle of the adult mouse forebrain is necessary and sufficient for the in vitro formation of clonally derived spheres of cells that exhibit stem cell properties such as selfmaintenance and the generation of a large number of progeny comprising the major cell types found in the central nervous system. Killing the constitutively proliferating cells of the subependyma in vivo has no effect on the number of stem cells isolated in vitro and induces a complete repopulation of the subependyma in vivo by relatively quiescent stem cells found within the subependyma. Depleting the relatively quiescent cell population within the subependyma in vivo results in a corresponding decrease in spheres formed in vitro and in the final number of constitutively proliferating cells in vivo, suggesting that a relatively quiescent subependymal cell is the in vivo source of neural stem cells.