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Cells in the astroglial lineage are neural stem cells

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Abstract

A common assumption of classical neuroscience was that neurons and glial cells were derived from separate pools of progenitor cells and that, once development was completed, no new neurons were produced. The subsequent disproving of the “no new neuron” dogma suggested that ongoing adult neurogenesis was supported by a population of multipotent neural stem cells. Two germinal regions within the adult mammalian brain were shown to contain neural progenitor cells: the subventricular zone (SVZ) along the walls of the lateral ventricles, and the subgranular zone (SGZ) within the dentate gyrus of the hippocampus. Surprisingly, when the primary progenitors (stem cells) of the new neurons in these regions were identified, they exhibited structural and biological markers of astrocytes. The architecture of these germinal regions and the pattern of division of neural stem cells have raised fundamental questions about the mechanism of adult neurogenesis. This review describes studies on the origin of adult neural stem cells, the features distinguishing them from astrocytes in non-germinal regions, and the control mechanisms of the proliferation and differentiation of these cells. Astrocytic adult neural stem cells are part of a developmental lineage extending from the neuroepithelium to radial glia to germinal astrocytes. Adult neural stem cells appear to be strongly influenced by their local microenvironment, while also contributing significantly to the architecture of these germinal zones. However, environment alone does not seem to be sufficient to induce non-germinal astrocytes to behave as neural stem cells. Although emerging evidence suggests that significant heterogeneity exists within populations of germinal zone astrocytes, the way that these differences are encoded remains unclear. The further characterization of these cells should eventually provide a body of knowledge central to the understanding of brain development and disease.

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Abbreviations

Ara-C:

cytosine-β-D-arabinofuranoside

BMP:

bone morphogenetic protein

BrdU:

bromodeoxyuridine

CNS:

central nervous system

EGF:

epidermal growth factor

EGFR:

EGF receptor

FGF:

fibroblast growth factor

GFAP:

glial fibrillary acidic protein

HSV-TK:

Herpes simplex virus thymidine kinase

LGE:

lateral ganglionic eminence

PGC:

periglomerular cell

PDGF:

platelet-derived growth factor

PDGFRα:

PDGF receptor alpha

RMS:

rostral migratory stream

SGZ:

subgranular zone

SVZ:

subventricular zone

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Acknowledgments

The authors wish to thank the members of the Alvarez-Buylla laboratory for helpful discussions and comments on the manuscript. Work in the Alvarez-Buylla laboratory is funded by grants from the NIH and Goldhirsh Foundation and a gift from John and Frances Bowes.

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Authors and Affiliations

  1. Department of Neurosurgery and Institute for Regeneration Medicine, University of California at San Francisco, San Francisco, CA, USA

    Rebecca A. Ihrie & Arturo Alvarez-Buylla

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  1. Rebecca A. Ihrie
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  2. Arturo Alvarez-Buylla
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Correspondence to Arturo Alvarez-Buylla.

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Work in the Alvarez-Buylla laboratory is supported by grants from the NIH and the Goldhirsh Foundation and by a gift from John and Frances Bowes. Rebecca Ihrie is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation. Arturo Alvarez-Buylla holds the Heather and Melanie Muss Endowed Chair in Neurosurgery.

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Ihrie, R.A., Alvarez-Buylla, A. Cells in the astroglial lineage are neural stem cells. Cell Tissue Res 331, 179–191 (2008). https://doi.org/10.1007/s00441-007-0461-z

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