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Science. 2018 Jun 1;360(6392). pii: eaar3131. doi: 10.1126/science.aar3131. Epub 2018 Apr 26.

Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.

Author information

1
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
2
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. aregev@broadinstitute.org schier@fas.harvard.edu.
4
Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA.
5
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. aregev@broadinstitute.org schier@fas.harvard.edu.
6
Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
7
FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
8
Biozentrum, University of Basel, Switzerland.
9
Allen Discovery Center for Cell Lineage Tracing, University of Washington, Seattle, WA 98195, USA.

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.

PMID:
29700225
PMCID:
PMC6247916
DOI:
10.1126/science.aar3131
[Indexed for MEDLINE]
Free PMC Article

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