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Increasing neural stem cell division asymmetry and quiescence are predicted to contribute to the age-related decline in neurogenesis.
Cell Rep. 25, 3231-3240.e8 (2018)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Adult Neurogenesis ; Computational Model ; Lineage Tracing ; Lineage Tree Simulation ; Model Averaging ; Moment Equations; Subventricular Zone; Lineage Progression; Embryonic Origin; Progenitors; Derivation; Criterion; Cycle; Pool
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 25,
Issue: 12,
Pages: 3231-3240.e8
Publisher
Cell Press
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
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Reviewing status
Peer reviewed