Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.
Helmholtz Zentrum München-German Research Center for Environmental Health, Unit Sensory Biology & Organogenesis, Neuherberg, Germany.
PLoS Biol. 2020 Dec 8;18(12):e3000708. doi: 10.1371/journal.pbio.3000708. eCollection 2020 Dec.
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.
静止和细胞周期进入的调节对于干细胞群体的维持至关重要。然而,调控机制还知之甚少。特别是,目前尚不清楚单个干细胞的活性如何在群体内协调,或者细胞是否以纯粹随机的方式分裂。我们通过分析斑马鱼端脑的成体神经干细胞(NSC)群体中的分裂事件来解决这个问题。对 36 个脑半球中的超过 80,000 个 NSCs 的空间统计和数学建模揭示了空间和时间上弱聚集的、非随机的分裂模式。分析两个时间点的分裂使我们能够计算推断细胞周期和 S 期长度。有趣的是,我们观察到大约 15%的新产生的 NSCs 中出现快速细胞周期再进入。在 NSC 群体的基于代理的模拟中,这种重新分裂的活动足以诱导与实验中观察到的匹配的聚集时空分裂模式。相比之下,忽略重新分裂会导致分裂细胞的随机时空分布。因此,分裂的干细胞的时空聚集可以仅从细胞的历史中出现。