Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis
Name
nihms-993376.pdf
Description
Accepted version
Size
1.83 MB
Format
Adobe PDF
Checksum (MD5)
779287136adf629341db50f787f25365
Author(s)
Regev, Aviv
Date Issued
June 2018
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Farrell, Jeffrey A. et al. “Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.” Science 360 (2018): eaar3131 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAR3131