A mosaic world: puzzles revealed by adult neural stem cell heterogeneity
Open accessAbstract
Neural stem cells (NSCs) reside in specialized niches in the adult mammalian brain. The ventricular-subventricular zone (V-SVZ), adjacent to the lateral ventricles, gives rise to olfactory bulb (OB) neurons, and some astrocytes and oligodendrocytes throughout life. In vitro assays have been widely used to retrospectively identify NSCs. However, cells that behave as stem cells in vitro do not reflect the identity, diversity, and behavior of NSCs in vivo. Novel tools including fluorescence activated cell sorting, lineage-tracing, and clonal analysis have uncovered multiple layers of adult V-SVZ NSC heterogeneity, including proliferation state and regional identity. In light of these findings, we reexamine the concept of adult NSCs, considering heterogeneity as a key parameter for analyzing their dynamics in vivo. V-SVZ NSCs form a mosaic of quiescent (qNSCs) and activated cells (aNSCs) that reside in regionally distinct microdomains, reflecting their regional embryonic origins, and give rise to specific subtypes of OB interneurons. Prospective purification and transcriptome analysis of qNSCs and aNSCs has illuminated their molecular and functional properties. qNSCs are slowly dividing, have slow kinetics of neurogenesis in vivo, can be recruited to regenerate the V-SVZ, and only rarely give rise to in vitro colonies. aNSCs are highly proliferative, undergo rapid clonal expansion of the neurogenic lineage in vivo, and readily form in vitro colonies. Key open questions remain about stem cell dynamics in vivo and the lineage relationship between qNSCs and aNSCs under homeostasis and regeneration, as well as context-dependent plasticity of regionally distinct adult NSCs under different external stimuli. WIREs Dev Biol 2016, 5:640-658. doi: 10.1002/wdev.248 For further resources related to this article, please visit the WIREs website.
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V-SVZ NSCs have a regional identity.
“Importantly, V-SVZ NSCs have a regional identity and give rise to specific subtypes of olfactory bulb interneurons or glia depending on their spatial location (Chaker et al., 2016; Fiorelli et al., 2015).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Chaker et al., 2016
The ventricular-subventricular zone (V-SVZ) harbors adult neural stem cells.
“The ventricular-subventricular zone (V-SVZ) harbors adult neural stem cells.”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Chaker et al., 2016
V-SVZ NSCs give rise to specific subtypes of olfactory bulb interneurons or glia depending on their spatial location.
“Importantly, V-SVZ NSCs have a regional identity and give rise to specific subtypes of olfactory bulb interneurons or glia depending on their spatial location (Chaker et al., 2016; Fiorelli et al., 2015).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Chaker et al., 2016
Adult V-SVZ NSCs co-exist in quiescent (qNSC) and actively dividing (aNSC) states.
“Adult V-SVZ NSCs co-exist in quiescent (qNSC) and actively dividing (aNSC) states (Chaker et al., 2016).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Chaker et al., 2016
V-SVZ NSCs are promptly recruited upon injury or under pathological conditions.
“Indeed, spatially distinct pools of NSCs can sense and respond to different local and long-range physiological signals to generate different types of OB interneurons (Paul et al., 2017), and V-SVZ NSCs are promptly recruited upon injury or under pathological conditions (Chaker et al., 2016).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Chaker et al., 2016
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Identification of region-specific astrocyte subtypes at single cell resolution
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Self-citationSingle-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages
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Campos, A. C., Fogaça, M. V., Scarante, F. F., Joca, S. R. L., Sales, A. J., Gomes, F. V., Sonego, A. B., Rodrigues, N. S., Galve-Roperh, I., & Guimarães, F. S. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00269 · Cited by 175 · see citing works
Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis
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Development of the mammalian main olfactory bulb
Tufo, C., Poopalasundaram, S., Dorrego-Rivas, A., Ford, M. C., Graham, A., & Grubb, M. S. (2022) · Development · doi:10.1242/dev.200210 · Cited by 75 · see citing works
- Authors
- Chaker, Z., Codega, P., & Doetsch, F.
- Affiliations
- University of Basel (CH)
- Columbia University (US)
- Corresponding author
- Doetsch, Fiona
- Venue
- WIREs Developmental Biology
- Publisher
- Wiley
- Published
- 2016-09-20
- Volume
- 5
- Issue
- 6
- Pages
- 640-658
- ISSN
- 1759-7684 (ISSN-L)
- 1759-7692
- PMC
- PMC5113677
- OpenAlex
- W2522918785
- Cited by
- 198
- References
- 128
- Citations by year
- 2026: 6 · 2025: 24 · 2024: 21 · 2023: 24 · 2022: 14 · 2021: 19 · 2020: 22 · 2019: 29 · 2018: 20 · 2017: 19
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Wiley Interdisciplinary Reviews Developmental Biology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- edoc (University of Basel) (submittedVersion)
- Funders
- National Institutes of Health (R01NS074039)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- adult neural stem cells, stem cell heterogeneity, ventricular-subventricular zone, olfactory bulb interneurons, quiescent neural stem cells, regional identity, lineage tracing, clonal analysis, stem cell niche, neurogenesis, stem cell regeneration, stem cell plasticity, transcriptome
- MeSH terms
- Adult, Cell Differentiation, Humans, Adult Stem Cells, Stem Cell Niche, Neurogenesis, Neural Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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