Neural Stem Cells Confer Unique Pinwheel Architecture to the Ventricular Surface in Neurogenic Regions of the Adult Brain

Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell stem cell (Impact Factor: 22.27). 10/2008; 3(3):265-78. DOI: 10.1016/j.stem.2008.07.004
Source: PubMed

ABSTRACT 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.

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    • "Ependymal cells form interdigitations, tight junctions and adherens junctions with each other to separate the SVZ from the cerebrospinal fluid of the ventricle cavity. On the other hand, NSCs are identified as a subpopulation of astrocytes called B1 astrocytes that differ from another subpopulation of non-neurogenic astrocytes (B2 astrocytes; Doetsch et al., 1997, 1999a; Han et al., 2008; Ihrie and Alvarez-Buylla, 2008; Mirzadeh et al., 2008; Gil-Perotin et al., 2009; Morrens et al., 2012). Briefly, astrocytes present bundles of intermediate filaments and light cytoplasm. "
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    ABSTRACT: Neural stem cells persist in the adult mammalian brain through life. The subventricular zone is the largest source of stem cells in the nervous system, and continuously generates new neuronal and glial cells involved in brain regeneration. During aging, the germinal potential of the subventricular zone suffers a widespread decline, but the causes of this turn down are not fully understood. This review provides a compilation of the current knowledge about the age-related changes in the neural stem cell population, as well as the fate of the newly generated cells in the aged brain. It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised. Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders. Further studies in this matter are required to improve our understanding and the current strategies for fighting neurological diseases associated with senescence.
    Frontiers in Cellular Neuroscience 09/2015; 9(365). DOI:10.3389/fncel.2015.00365 · 4.29 Impact Factor
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    • "B1 cells have many features of astrocytes (Doetsch et al., 1999) and retain expression of Nestin, BLBP, GLAST, and Sox2 (Lagace et al., 2007; Giachino et al., 2014), which are also expressed in radial glia cells (RGs), the NSCs in the developing brain. Indeed, B1 cells are derived from RGs (Merkle et al., 2004) and display epithelial apico-basal organization reminiscent of RG morphology (Mirzadeh et al., 2008). These observations have suggested a linear NSC lineage from neuroepithelial cells to RGs to adult B1 cells (Alvarez-Buylla et al., 2001; Temple, 2001; Kriegstein and Alvarez-Buylla, 2009). "
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    ABSTRACT: Adult neural stem/progenitor (B1) cells within the walls of the lateral ventricles generate different types of neurons for the olfactory bulb (OB). The location of B1 cells determines the types of OB neurons they generate. Here we show that the majority of mouse B1 cell precursors are produced between embryonic days (E) 13.5 and 15.5 and remain largely quiescent until they become reactivated postnatally. Using a retroviral library carrying over 100,000 genetic tags, we found that B1 cells share a common progenitor with embryonic cells of the cortex, striatum, and septum, but this lineage relationship is lost before E15.5. The regional specification of B1 cells is evident as early as E11.5 and is spatially linked to the production of neurons that populate different areas of the forebrain. This study reveals an early embryonic regional specification of postnatal neural stem cells and the lineage relationship between them and embryonic progenitor cells. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 06/2015; 161(7):1644-1655. DOI:10.1016/j.cell.2015.05.041 · 32.24 Impact Factor
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    • "These age-dependent metabolic changes were reproduced in young astrocytes upon exposure to inflammatory cytokines (IL-1b and TNF-a), which may result in neuroinflammatory and degenerative responses. Alternatively, the elevated GFAP signal documented in the ependymal layer of aged and young MARCKS-cKO mice may be due to increase in astrocytic processes of adult and aging stem cells that are in contact with the ventricles and nearby blood vessels (Doetsch et al., 1999; Mirzadeh et al., 2008). Future studies will be required to dissect the mechanisms for the integration of astrocytes in the ependymal surface and identifying their role in the EC layer. "
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    ABSTRACT: Ependymal cells (ECs) form a barrier responsible for selective movement of fluids and molecules between the cerebrospinal fluid and the central nervous system. Here, we demonstrate that metabolic and barrier functions in ECs decline significantly during aging in mice. The longevity of these functions in part requires the expression of the myristoylated alanine-rich protein kinase C substrate (MARCKS). Both the expression levels and subcellular localization of MARCKS in ECs are markedly transformed during aging. Conditional deletion of MARCKS in ECs induces intracellular accumulation of mucins, elevated oxidative stress, and lipid droplet buildup. These alterations are concomitant with precocious disruption of ependymal barrier function, which results in the elevation of reactive astrocytes, microglia, and macrophages in the interstitial brain tissue of young mutant mice. Interestingly, similar alterations are observed during normal aging in ECs and the forebrain interstitium. Our findings constitute a conceptually new paradigm in the potential role of ECs in the initiation of various conditions and diseases in the aging brain. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
    Aging cell 05/2015; 14(5). DOI:10.1111/acel.12354 · 6.34 Impact Factor
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