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Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain
Open accessAbstract
Neural stem cells reside in the subventricular zone (SVZ) of the adult mammalian brain. This germinal region, which continually generates new neurons destined for the olfactory bulb, is composed of four cell types: migrating neuroblasts, immature precursors, astrocytes, and ependymal cells. Here we show that SVZ astrocytes, and not ependymal cells, remain labeled with proliferation markers after long survivals in adult mice. After elimination of immature precursors and neuroblasts by an antimitotic treatment, SVZ astrocytes divide to generate immature precursors and neuroblasts. Furthermore, in untreated mice, SVZ astrocytes specifically infected with a retrovirus give rise to new neurons in the olfactory bulb. Finally, we show that SVZ astrocytes give rise to cells that grow into multipotent neurospheres in vitro. We conclude that SVZ astrocytes act as neural stem cells in both the normal and regenerating brain.
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“Radial glial cells, stem cell precursors, and astrocytes - all reported to express GFAP (reviewed in ref.26) - are found in the dentate gyrus2,27,28.”
From Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB (2021) · cites this paper as [28]
In the citing paper
“After this period of symmetric divisions, these progenitor cells — also known as radial glia — divide asymmetrically, generating postmitotic excitatory neurons that will migrate to their final location in the cerebral cortex by using the basal process of the radial glial cell as a scaffold55–58.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [58]
In the citing paper
“Adult V-SVZ NSCs are radial cells with many hallmarks of astrocytes (Doetsch et al., 1999).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Doetsch et al., 1999
In the citing paper
“Upon activation, they give rise to transit amplifying cells (TACs), which in turn generate neuroblasts (NBs) that migrate to the olfactory bulb (Doetsch et al., 1999).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Doetsch et al., 1999
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Tamura, Y., Kataoka, Y., Cui, Y., Takamori, Y., Watanabe, Y., & Yamada, H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05617.x · Cited by 104
Metadata
- Authors
- Doetsch, F., Caillé, I., Lim, D. A., García-Verdugo, J. M., & Alvarez-Buylla, A.
- Affiliations
- Rockefeller University (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 97
- Issue
- 6
- Pages
- 703-716
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2165867905
- Cited by
- 3,898
- References
- 77
- Citations by year
- 2026: 31 · 2025: 71 · 2024: 54 · 2023: 79 · 2022: 94 · 2021: 110 · 2020: 105 · 2019: 113 · 2018: 110 · 2017: 134 · 2016: 135 · 2015: 177 · 2014: 154 · 2013: 180 · 2012: 243
- FWCI
- 26.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 07739, T32GM007739)
- National Institute of Neurological Disorders and Stroke (NS-28478)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD32116)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- subventricular zone, astrocytes, neural stem cells, adult neurogenesis, olfactory bulb, neuroblast migration, ependymal cells, retroviral labeling, neurospheres, stem cell self-renewal
- MeSH terms
- Animals, Astrocytes, Brain, Cerebral Ventricles, Chick Embryo, Glial Fibrillary Acidic Protein, Male, Olfactory Bulb, Regeneration, Stem Cells, Mice
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