Increasing Neural Stem Cell Division Asymmetry and Quiescence Are Predicted to Contribute to the Age-Related Decline in Neurogenesis
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Abstract
Adult murine neural stem cells (NSCs) generate neurons in drastically declining numbers with age. How cellular dynamics sustain neurogenesis and how alterations with age may result in this decline are unresolved issues. We therefore clonally traced NSC lineages using confetti reporters in young and middle-aged adult mice. To understand the underlying mechanisms, we derived mathematical models that explain observed clonal cell type abundances. The best models consistently show self-renewal of transit-amplifying progenitors and rapid neuroblast cell cycle exit. In middle-aged mice, we identified an increased probability of asymmetric stem cell divisions at the expense of symmetric differentiation, accompanied by an extended persistence of quiescence between activation phases. Our model explains existing longitudinal population data and identifies particular cellular properties underlying adult NSC homeostasis and the aging of this stem cell compartment.
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Stem cell heterogeneity during ageing may be due to a decrease in symmetrical divisions and an increase in asymmetrical divisions in old NSCs.
“Such stem cell heterogeneity during ageing may be due to a decrease in symmetrical divisions and an increase in asymmetrical divisions in old NSCs27,28.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [28]
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- Authors
- Bast, L., Calzolari, F., Strasser, M. K., Hasenauer, J., Theis, F. J., Ninkovic, J., & Marr, C.
- Affiliations
- Helmholtz Munich (DE)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Calzolari, Filippo
- Ninkovic, Jovica
- Marr, Carsten
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 25
- Issue
- 12
- Pages
- 3231-3240.e8
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2904523538
- Cited by
- 50
- References
- 62
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 10 · 2021: 4 · 2020: 10 · 2019: 5
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-nd)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsche Forschungsgemeinschaft (CRC1243)
- 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, aging, asymmetric cell division, stem cell quiescence, self-renewal, clonal tracing, mathematical modeling, stem cell homeostasis, adult neurogenesis
- MeSH terms
- Aging, Animals, Cell Cycle, Clone Cells, Computer Simulation, Models, Biological, Stochastic Processes, Reproducibility of Results, Cell Lineage, Mice, Neurogenesis, Neural Stem Cells, Asymmetric Cell Division
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