Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis. Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis

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 branchpoints contained cells expressing 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 to reconstruct complex developmental trees from single-cell transcriptomes. This SuperSeries is composed of the SubSeries listed below. Overall design: Drop-seq analysis of wild-type embryos (38,731 cells, 12 timepoints, 28 samples total, 20-40 embryos per sample), SMART-seq2 analysis of wild-type and MZoep mutant embryos (52 wild-type and 364 MZoep cells from 50% epiboly stage), and 10X single-cell sequencing analysis of WT and MZoep mutant embryos (3,000 WT and 2,200 MZoep cells from 6-somites stage).