Subtle Changes in Clonal Dynamics Underlie the Age-Related Decline in Neurogenesis
SUMMARYNeural stem cells in the adult murine brain have only a limited capacity to self-renew, and the number of neurons they generate drastically declines with age. How cellular dynamics sustain neurogenesis and how alterations with age may result in this decline, are both unresolved issues. Therefore, we clonally traced neural stem cell lineages using confetti reporters in young and middle-aged adult mice. To understand underlying mechanisms, we derived mathematical population models of adult neurogenesis that explain the observed clonal cell type abundances. Models fitting the data best consistently show self renewal of transit amplifying progenitors and rapid neuroblast cell cycle exit.…
Increasing Neural Stem Cell Division Asymmetry and Quiescence Are Predicted to Contribute to the Age-Related Decline in Neurogenesis.
Summary: 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 di…
NG2-Glia Transiently Overcome Their Homeostatic Network and Contribute to Wound Closure After Brain Injury
In the adult brain, NG2-glia represent a cell population that responds to injury. To further investigate if, how and why NG2-glia are recruited to the injury site, we analyzed in detail the long-term reaction of NG2-glia after a lesion by time-lapse two-photon in vivo microscopy. Live imaging over several weeks of GFP-labeled NG2-glia in the stab wounded cerebral cortex revealed their fast and heterogeneous reaction, including proliferation, migration, polarization, hypertrophy, or a mixed response, while a small subset of cells remained unresponsive. At the peak of the reaction, 2–4 days after the injury, NG2-glia accumulated around and within the lesion core, overcoming the homeostatic co…