Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Unit on Cell Specification and Differentiation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20814, USA.
Neuron. 2020 Dec 23;108(6):1058-1074.e6. doi: 10.1016/j.neuron.2020.09.023. Epub 2020 Oct 16.
Neurogenesis comprises many highly regulated processes including proliferation, differentiation, and maturation. However, the transcriptional landscapes underlying brain development are poorly characterized. We describe a developmental single-cell catalog of ∼220,000 zebrafish brain cells encompassing 12 stages from embryo to larva. We characterize known and novel gene markers for ∼800 clusters and provide an overview of the diversification of neurons and progenitors across these time points. We also introduce an optimized GESTALT lineage recorder that enables higher expression and recovery of Cas9-edited barcodes to query lineage segregation. Cell type characterization indicates that most embryonic neural progenitor states are transitory and transcriptionally distinct from neural progenitors of post-embryonic stages. Reconstruction of cell specification trajectories reveals that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo. The zebrafish brain development atlas provides a resource to define and manipulate specific subsets of neurons and to uncover the molecular mechanisms underlying vertebrate neurogenesis.
神经发生包括许多高度调控的过程，包括增殖、分化和成熟。然而，大脑发育的转录景观特征描述很差。我们描述了一个约 22 万个斑马鱼大脑细胞的发育单细胞目录，涵盖了从胚胎到幼虫的 12 个阶段。我们对约 800 个簇的已知和新的基因标记进行了特征描述，并提供了这些时间点上神经元和祖细胞多样化的概述。我们还引入了一种优化的 GESTALT 谱系记录器，该记录器能够更高地表达和恢复 Cas9 编辑的条形码，以查询谱系分离。细胞类型特征表明，大多数胚胎神经前体细胞状态是短暂的，与胚胎后阶段的神经前体细胞在转录上是不同的。细胞特化轨迹的重建表明，晚期视网膜神经前体细胞在转录上与胚胎中观察到的细胞状态重叠。斑马鱼大脑发育图谱提供了一个资源，可以定义和操纵特定的神经元亚群，并揭示脊椎动物神经发生的分子机制。
