Reoccurring neural stem cell divisions in the adult zebrafish telencephalon are sufficient for the emergence of aggregated spatiotemporal patterns

Abstract

Regulation of quiescence and cell cycle entry is pivotal for the maintenance of stem cell populations. Regulatory mechanisms, however, are poorly understood. In particular, it is unclear how the activity of single stem cells is coordinated within the population or if cells divide in a purely random fashion. We addressed this issue by analyzing division events in an adult neural stem cell (NSC) population of the zebrafish telencephalon. Spatial statistics and mathematical modeling of over 80,000 NSCs in 36 brain hemispheres revealed weakly aggregated, nonrandom division patterns in space and time. Analyzing divisions at 2 time points allowed us to infer cell cycle and S-phase lengths computationally. Interestingly, we observed rapid cell cycle reentries in roughly 15% of newly born NSCs. In agent-based simulations of NSC populations, this redividing activity sufficed to induce aggregated spatiotemporal division patterns that matched the ones observed experimentally. In contrast, omitting redivisions leads to a random spatiotemporal distribution of dividing cells. Spatiotemporal aggregation of dividing stem cells can thus emerge solely from the cells’ history.

Dynamic spatiotemporal coordination of neural stem cell fate decisions occurs through local feedback in the adult vertebrate brain

“…We exclusively considered de novo activation/division events from quiescence, disregarding the second or third division events of NSCs that rapidly divide repeatedly, for two reasons. First, rapid consecutive NSC divisions without intervening quiescence phases generate transiently clustered aNSCs ( Lupperger et al., 2020 ), but these events are rare (14 tracks in a total of 117 dividing tracks followed, 12% of NSCs) ( Figure S5 ). Second, the initial NSC activation decision conditions both neurogenesis and the maintenance of NSC numbers.…”

Agent-based models in cellular systems

“…Furthermore, CompuCell3D provided examples for self-organization in work on polarization [81] and studies of physical forces [82] in migrating cells. Morpheus was used to describe pattern formations in the telencephalon of adult zebrafish [83] and was also used to study growth of the Drosophila wing via cell recruitment [84]. PhysiCell recently provided insights to formation of patterns in tumour spheroids [56].…”