Zebrafish Neurogenetics Unit, Institut Pasteur, UMR3738, CNRS, Team supported by the Ligue Nationale Contre le Cancer, Paris 75015, France.
Université Paris-Saclay, Ecole Doctorale Biosigne, Le Kremlin-Bicêtre, France.
Sci Adv. 2020 Apr 29;6(18):eaaz5424. doi: 10.1126/sciadv.aaz5424. eCollection 2020 May.
The cellular basis and extent of neural stem cell (NSC) self-renewal in adult vertebrates, and their heterogeneity, remain controversial. To explore the functional behavior and dynamics of individual NSCs, we combined genetic lineage tracing, quantitative clonal analysis, intravital imaging, and global population assessments in the adult zebrafish telencephalon. Our results are compatible with a model where adult neurogenesis is organized in a hierarchy in which a subpopulation of deeply quiescent reservoir NSCs with long-term self-renewal potential generate, through asymmetric divisions, a pool of operational NSCs activating more frequently and taking stochastic fates biased toward neuronal differentiation. Our data further suggest the existence of an additional, upstream, progenitor population that supports the continuous generation of new reservoir NSCs, thus contributing to their overall expansion. Hence, we propose that the dynamics of vertebrate neurogenesis relies on a hierarchical organization where growth, self-renewal, and neurogenic functions are segregated between different NSC types.
神经干细胞（NSC）在成年脊椎动物中的自我更新的细胞基础和程度，以及它们的异质性，仍然存在争议。为了探索单个 NSC 的功能行为和动力学，我们在成年斑马鱼端脑中结合了遗传谱系追踪、定量克隆分析、活体成像和整体群体评估。我们的结果与以下模型一致：成年神经发生是在一个层次结构中组织的，其中一小部分深度静止的储备 NSCs 具有长期自我更新潜力，通过不对称分裂产生一个更频繁激活的操作 NSCs 池，并随机偏向神经元分化。我们的数据还表明存在一个额外的上游祖细胞群体，它支持新储备 NSCs 的持续产生，从而有助于它们的整体扩增。因此，我们提出，脊椎动物神经发生的动力学依赖于一个层次化的组织，其中不同的 NSC 类型之间分离了生长、自我更新和神经发生功能。
