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The Glial Nature of Embryonic and Adult Neural Stem Cells
Open accessAbstract
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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“GFAP is also expressed by progenitor cells15 and its expression depends on developmental stages16,17.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [15]
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In the citing paper
“In particular, and by taking advantage of Btg2 and Tubb3 expression, our group has generated a combinatorial, double-reporter mouse line in which RFP and or GFP expression allowed the isolation specifically of PP, DP and N based on their endogenous fluorescence (RFP-, RFP+ and GFP+, respectively) (31).”
From MicroRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis (2020) · cites this paper as [31]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Unsurprisingly, when analyzing the expression pattern of the host genes of switch miRNAs (data retrieved from ( 31)), we found a high degree of overlap in their differential expression within different cell populations (Figure 3).”
From MicroRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis (2020) · cites this paper as [31]
Experimental — accuracy not yet measuredIn the citing paper
“There is evidence of neurogenesis from adult neural stem cells deriving from the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus, that can give rise to neurons, oligodendrocytes and astrocytes [107,108].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [108]
In the citing paper
“The predicted progenitors expressed proliferation (Mki67) and known markers (Pax6, Rspo2/3, Wnt5a/3a/1, Fabp7, clusters 7 and 8 in Figure 2A,B S2B; STAR Methods), previously reported for precursors of ependymal cells and cortical neurons (Kriegstein and Alvarez-Buylla, 2009), with Wnt1 having the most specific expression (Figure S2G).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Kriegstein and Alvarez-Buylla, 2009
In the citing paper
“In embryos, subsets of glial cells expressed markers of neural progenitor/stem-like cells (e.g. Pax6, Nes, Sox2, Rspo2/3) or of oligodendrocyte precursor cells (OPCs, e.g. Olig1, Olig2) (Kriegstein and Alvarez-Buylla, 2009) (Figure 2A, S2A,B).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Kriegstein and Alvarez-Buylla, 2009
In the citing paper
“Validation and use of this mouse line revealed to be very powerful in the identification of several new genes and biological processes regulating cortical development (31).”
From MicroRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis (2020) · cites this paper as [31]
In the citing paper
“our group previously concluded that a transient up-or down-regulation specifically in DP compared to both their PP progenitors and N progeny (on-and off-switch transcripts, respectively) represented a hallmark of functional commitment to the neurogenic lineage (31,36).”
From MicroRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis (2020) · cites this paper as [31]
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Semple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M., & Noble-Haeusslein, L. J. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.001 · Cited by 2,132
Verkhratsky, A., & Nedergaard, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00042.2016 · Cited by 1,678
Metadata
- Authors
- Kriegstein, A., & Alvarez-Buylla, A.
- Affiliations
- University of California, San Francisco (US)
- The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Departments of Neurology, Neurological Surgery, and School of Medicine, University of California, San Francisco, California 94143-0525;,
- ORCID
- Kriegstein, Arnold
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2009-06-01
- Volume
- 32
- Issue
- 1
- Pages
- 149-184
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC3086722
- OpenAlex
- W2172266256
- Cited by
- 2,475
- References
- 263
- Citations by year
- 2026: 87 · 2025: 141 · 2024: 138 · 2023: 131 · 2022: 133 · 2021: 168 · 2020: 162 · 2019: 147 · 2018: 166 · 2017: 155 · 2016: 162 · 2015: 129 · 2014: 167 · 2013: 172 · 2012: 155
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS035710, R01NS028478, R01NS021223)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neural stem cells, radial glia, astrocytes, intermediate progenitor cells, transit amplifying cells, neuronal lineage, neuroepithelium, adult neurogenesis, brain development, lineage tracing, brain repair
- MeSH terms
- Animals, Cell Differentiation, Central Nervous System, Humans, Neuroglia, Neurons, Stem Cells, Gene Expression Regulation, Developmental, Cell Lineage, Adult Stem Cells, Neurogenesis
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