The Glial Nature of Embryonic and Adult Neural Stem Cells

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, United States
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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    • "in the hippocampal DG have the ability to generate self-renewing neural stem cells possessing multipotency[28]. Adult neurogenesis occurs in three discrete stages, proliferation of NSCs, cell survival, and neuronal differentiation, which are affected by various factors such as hormones, growth factors, enriched environment, stress, drugs, and pathological stimulation[29,30]. The process in the DG affected by these factors is associated with cognitive functions including learning and memory[31]. "
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    ABSTRACT: Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-κB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-κB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.
    Full-text · Article · Jan 2016 · Korean Journal of Physiology and Pharmacology
    • "Another important diference in organization of glia between echinoderms and chordates is that the radial glia constitute the only major glial cell type in the adult cnS of echinoderms. in higher vertebrates, radial glia predominate in embryogenesis, but then mostly disappear from the mature nervous system by giving rise to the multitude of more specialized cell types including astrocytes, ependymocytes, oligodendrocytes, and also neural stem/progenitor cells in restricted zones of adult neurogenesis (Kriegstein and Alvarez-Buylla 2009, malatesta et al. 2008, Spassky et al. 2005). lower vertebrates retain radial glia in their adult cnS, but even in this case the radial glial cells co-exist with other abundant specialized glia, such as oligodendrocytes (tanaka and ferretti 2009, zamora 1978). "

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    • "T he definition of astrocyte functions and developmental potential, in particular in relation to neural stem cells, is still a dynamic area of research (Bayraktar et al., 2015; Gotz et al., 2015; Robel et al., 2011). Astrocytes and neural stem cells (NSC) share several phenotypic and functional features (Doetsch et al., 1999; Kriegstein and Alvarez-Buylla, 2009; Levitt and Rakic, 1980; Seri et al., 2001). Moreover, some types of NSC (radial glia or astrocytes from the subventricular zone) have been categorized as members of the heterogeneous group of astrocytes, due to their expression of the glial fibrillary acidic protein (GFAP), the most frequently used astrocyte marker (Eng et al., 2000; Ihrie and Alvarez- Buylla, 2008; Steindler and Laywell, 2003). "
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    ABSTRACT: Availability of homogeneous astrocyte populations would facilitate research concerning cell plasticity (metabolic and transcriptional adaptations; innate immune responses) and cell cycle reactivation. Current protocols to prepare astrocyte cultures differ in their final content of immature precursor cells, preactivated cells or entirely different cell types. A new method taking care of all these issues would improve research on astrocyte functions. We found here that the exposure of a defined population of pluripotent stem cell-derived neural stem cells (NSC) to BMP4 results in pure, nonproliferating astrocyte cultures within 24-48 h. These murine astrocytes generated from embryonic stem cells (mAGES) expressed the positive markers GFAP, aquaporin 4 and GLT-1, supported neuronal function, and acquired innate immune functions such as the response to tumor necrosis factor and interleukin 1. The protocol was applicable to several normal or disease-prone pluripotent cell lines, and the corresponding mAGES all exited the cell cycle and lost most of their nestin expression, in contrast to astrocytes generated by serum-addition or obtained as primary cultures. Comparative gene expression analysis of mAGES and NSC allowed quantification of differences between the two cell types and a definition of an improved marker set to define astrocytes. Inclusion of several published data sets in this transcriptome comparison revealed the similarity of mAGES with cortical astrocytes in vivo. Metabolic analysis of homogeneous NSC and astrocyte populations revealed distinct neurochemical features: both cell types synthesized glutamine and citrate, but only mature astrocytes released these metabolites. Thus, the homogeneous cultures allowed an improved definition of NSC and astrocyte features. GLIA 2015.
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