Axonal Control of the Adult Neural Stem Cell Niche (original) (raw)
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Cell Stem Cell, 2008
Neural stem cells (NSCs, B1 cells) are retained in the walls of the adult lateral ventricles but, unlike embryonic NSCs, are displaced from the ventricular zone (VZ) into the subventricular zone (SVZ) by ependymal cells. Apical and basal compartments, which in embryonic NSCs play essential roles in self-renewal and differentiation, are not evident in adult NSCs. Here we show that SVZ B1 cells in adult mice extend a minute apical ending to directly contact the ventricle and a long basal process ending on blood vessels. A closer look at the ventricular surface reveals a striking pinwheel organization specific to regions of adult neurogenesis. The pinwheel's core contains the apical endings of B1 cells and in its periphery two types of ependymal cells: multiciliated (E1) and a type (E2) characterized by only two cilia and extraordinarily complex basal bodies. These results reveal that adult NSCs retain fundamental epithelial properties, including apical and basal compartmentalization, significantly reshaping our understanding of this adult neurogenic niche.
The Molecular Profiles of Neural Stem Cell Niche in the Adult Subventricular Zone
PLoS ONE, 2012
Neural stem cells (NSCs) reside in a unique microenvironment called the neurogenic niche and generate functional new neurons. The neurogenic niche contains several distinct types of cells and interacts with the NSCs in the subventricular zone (SVZ) of the lateral ventricle. While several molecules produced by the niche cells have been identified to regulate adult neurogenesis, a systematic profiling of autocrine/paracrine signaling molecules in the neurogenic regions involved in maintenance, self-renewal, proliferation, and differentiation of NSCs has not been done. We took advantage of the genetic inducible fate mapping system (GIFM) and transgenic mice to isolate the SVZ niche cells including NSCs, transit-amplifying progenitors (TAPs), astrocytes, ependymal cells, and vascular endothelial cells. From the isolated cells and microdissected choroid plexus, we obtained the secretory molecule expression profiling (SMEP) of each cell type using the Signal Sequence Trap method. We identified a total of 151 genes encoding secretory or membrane proteins. In addition, we obtained the potential SMEP of NSCs using cDNA microarray technology. Through the combination of multiple screening approaches, we identified a number of candidate genes with a potential relevance for regulating the NSC behaviors, which provide new insight into the nature of neurogenic niche signals.
Genetic targeting of neurogenic precursors in the adult forebrain ventricular epithelium
Life Science Alliance, 2020
The ventricular epithelium of the adult forebrain is a heterogeneous cell population that is a source of both quiescent and activated neural stem cells (qNSCs and aNSCs, respectively). We genetically targeted a subset of ventricle-contacting, glial fibrillary acidic protein (GFAP)-expressing cells, to study their involvement in qNSC/aNSC–mediated adult neurogenesis. Ventricle-contacting GFAP+ cells were lineage-traced beginning in early adulthood using adult brain electroporation and produced small numbers of olfactory bulb neuroblasts until at least 21 mo of age. Notably, electroporated GFAP+ neurogenic precursors were distinct from both qNSCs and aNSCs: they did not give rise to neurosphere-forming aNSCs in vivo or after extended passaging in vitro and they were not recruited during niche regeneration. GFAP+ cells with these properties included a FoxJ1+GFAP+ subset, as they were also present in an inducible FoxJ1 transgenic lineage-tracing model. Transiently overexpressing Mash1 i...
Frontiers in Cell and Developmental Biology, 2022
Neurogenesis persists in selected regions of the adult mouse brain; among them, the ventricular-subventricular zone (V-SVZ) of the lateral ventricles represents a major experimental paradigm due to its conspicuous neurogenic output. Postnatal V-SVZ neurogenesis is maintained by a resident population of neural stem cells (NSCs). Although V-SVZ NSCs are largely quiescent, they can be activated to enter the cell cycle, self-renew and generate progeny that gives rise to olfactory bulb interneurons. These adult-born neurons integrate into existing circuits to modify cognitive functions in response to external stimuli, but cells shed by V-SVZ NSCs can also reach injured brain regions, suggesting a latent regenerative potential. The V-SVZ is endowed with a specialized microenvironment, which is essential to maintain the proliferative and neurogenic potential of NSCs, and to preserve the NSC pool from exhaustion by finely tuning their quiescent and active states. Intercellular communication...
2020
ABSTRACTNeural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ) contribute to olfaction by being the origin of most adult-born olfactory bulb (OB) interneurons. The current consensus maintains that adult NSCs are radial glialike progenitors apically contacting the lateral ventricle and generating intermediate progenitors migrating at the basal V-SVZ. Whether basal NSCs are present in the V-SVZ is unknown. We here used genetic tagging of NSCs in vivo and additional labelling approaches to reveal that basal NSCs lacking apical attachment represent the largest NSC type in the postnatal V-SVZ from birth onwards. Despite dividing faster than their apical counterpart, basal NSCs still undergo long-term self-renewal and quiescence. Unlike apical NSCs, they are largely devoid of primary cilia and Prominin-1, Nestin and glial fibrillary acidic protein (GFAP) immunoreactivity. Six weeks after viral tagging of apical cells, few descendant cells were detected in the basal V-SVZ,...
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.,