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

PLoS Biol. 2020 Dec 8;18(12):e3000708. doi: 10.1371/journal.pbio.3000708. eCollection 2020 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism
  • Animals
  • Cell Cycle / physiology
  • Cell Differentiation / physiology*
  • Cell Division / physiology
  • Cell Proliferation / physiology
  • Models, Theoretical
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / physiology
  • Neurogenesis / physiology
  • Signal Transduction / physiology
  • Telencephalon / cytology
  • Telencephalon / growth & development*
  • Telencephalon / metabolism
  • Zebrafish / growth & development
  • Zebrafish Proteins / metabolism

Substances

  • Zebrafish Proteins

Grants and funding

V.L. was funded by the Bundesministerium für Bildung und Forschung (BMBF, https://www.gesundheitsforschung-bmbf.de/de/micmode-i2t-modulare-bildanalyseplattform-zur-integration-von-mikroskopischen-bildbasierten-7611.php), grant 01ZX1710A-F (Micmode-I2T). C.M. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 866411). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.