The Glial Nature of Embryonic and Adult Neural Stem Cells

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Neurology, University of California, San Francisco, California 94143-0525, USA.
Annual Review of Neuroscience (Impact Factor: 19.32). 08/2009; 32(1):149-84. DOI: 10.1146/annurev.neuro.051508.135600
Source: PubMed


Glial cells were long considered end products of neural differentiation, specialized supportive cells with an origin very different from that of neurons. New studies have shown that some glial cells--radial glia (RG) in development and specific subpopulations of astrocytes in adult mammals--function as primary progenitors or neural stem cells (NSCs). This is a fundamental departure from classical views separating neuronal and glial lineages early in development. Direct visualization of the behavior of NSCs and lineage-tracing studies reveal how neuronal lineages emerge. In development and in the adult brain, many neurons and glial cells are not the direct progeny of NSCs, but instead originate from transit amplifying, or intermediate, progenitor cells (IPCs). Within NSCs and IPCs, genetic programs unfold for generating the extraordinary diversity of cell types in the central nervous system. The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated. Identification of NSCs and IPCs is critical to understand brain development and adult neurogenesis and to develop new strategies for brain repair.

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Available from: Arnold R Kriegstein, Dec 16, 2014
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    • "Since the discovery of neural stem cells (NSCs) (Reynolds and Weiss 1992), we realized that the aforementioned rules of CNS stability have a main exception in two brain regions: the forebrain subventricular zone (SVZ) (Lois and Alvarez-Buylla 1994) and the hippocampal subgranular zone (SGZ) (Gage 2000). These " adult neurogenic sites " are remnants of the embryonic germinal layers (although indirectly for the SGZ, which forms ectopically from the embryonic germinative matrix), which retain stem/ progenitor cells within a special microenvironment , a " niche, " allowing and regulating NSC activity (Kriegstein and Alvarez-Buylla 2009). "
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    ABSTRACT: Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.
    Cold Spring Harbor perspectives in biology 09/2015; DOI:10.1101/cshperspect.a018846 · 8.68 Impact Factor
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    • "Corticogenesis from PSCs is an interesting case study, as it is the brain structure that probably displays the highest level of complexity, both in terms of cell diversity and connectivity, raising the question of the extent to which it can be reproduced in simplistic settings of PSC differentiation. The mammalian cerebral cortex consists of six layers of excitatory and inhibitory neurons, the former being generated by radial glial progenitors (RGs) in the ventricular zone (VZ) of the dorsal telencephalon (Kriegstein and Alvarez-Buylla, 2009; Taverna et al., 2014), whereas the latter are produced in the ventral telencephalon and subsequently migrate to the dorsal telencephalon (Fig. 2A) (DeFelipe et al., 2013; Greig et al., 2013; Sur and Rubenstein, 2005). Cortical RGs generate neurons directly or indirectly through the transit amplification of progenitors [such as basal progenitors (BPs)] in the subventricular zone (SVZ) (Haubensak et al., 2004; Miyata et al., 2004; Noctor et al., 2004) (Fig. 2A). "
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    ABSTRACT: The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution.
    Development 09/2015; 142(18):3138-3150. DOI:10.1242/dev.120568 · 6.46 Impact Factor
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    • "It is known that NSCs within the SVZ derive from embryonic radial glia cells ( Merkle et al . , 2004 ; Kriegstein and Alvarez - Buylla , 2009 ; Morrens et al . , 2012 ; Fuentealba et al . "
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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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