Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Science. 2018 Jun 1;360(6392). doi: 10.1126/science.aar3131. Epub 2018 Apr 26.
During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula. Analysis of Nodal signaling mutants revealed that their transcriptomes were canalized into a subset of wild-type transcriptional trajectories. Some wild-type developmental branch points contained cells that express genes characteristic of multiple fates. These cells appeared to trans-specify from one fate to another. These findings reconstruct the transcriptional trajectories of a vertebrate embryo, highlight the concurrent canalization and plasticity of embryonic specification, and provide a framework with which to reconstruct complex developmental trees from single-cell transcriptomes.
在胚胎发生过程中，细胞通过转录状态的转变获得不同的命运。为了揭示斑马鱼胚胎发生过程中的这些转录轨迹，我们对 38731 个细胞进行了测序，并开发了 URD，一种基于模拟扩散的计算重构方法。URD 通过早期体节形成、沿这些轨迹的基因表达以及它们在囊胚中的空间起源，鉴定了 25 种细胞类型的轨迹。对 Nodal 信号突变体的分析表明，它们的转录组被集中到野生型转录轨迹的一个子集。一些野生型发育分支点包含表达多种命运特征基因的细胞。这些细胞似乎从一种命运转变为另一种命运。这些发现重建了脊椎动物胚胎的转录轨迹，突出了胚胎发生特化的同时集中化和可塑性，并提供了一个从单细胞转录组重建复杂发育树的框架。
