Cited by 198Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationCongenital heart defects research

A mosaic world: puzzles revealed by adult neural stem cell heterogeneity

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Chaker, Zayna, Codega, Paolo, Doetsch, Fiona·2016·WIREs Developmental Biology

Abstract

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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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
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
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

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