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Nature. 2019 Feb;566(7745):490-495. doi: 10.1038/s41586-019-0933-9. Epub 2019 Feb 20.

A single-cell molecular map of mouse gastrulation and early organogenesis.

Author information

1
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
2
Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
3
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
4
The Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
5
Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK.
6
Epigenetics Programme, Babraham Institute, Cambridge, UK.
7
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
8
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
9
Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK.
10
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. john.marioni@cruk.cam.ac.uk.
11
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. john.marioni@cruk.cam.ac.uk.
12
EMBL-European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK. john.marioni@cruk.cam.ac.uk.
13
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. bg200@cam.ac.uk.
14
Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. bg200@cam.ac.uk.

Abstract

Across the animal kingdom, gastrulation represents a key developmental event during which embryonic pluripotent cells diversify into lineage-specific precursors that will generate the adult organism. Here we report the transcriptional profiles of 116,312 single cells from mouse embryos collected at nine sequential time points ranging from 6.5 to 8.5 days post-fertilization. We construct a molecular map of cellular differentiation from pluripotency towards all major embryonic lineages, and explore the complex events involved in the convergence of visceral and primitive streak-derived endoderm. Furthermore, we use single-cell profiling to show that Tal1-/- chimeric embryos display defects in early mesoderm diversification, and we thus demonstrate how combining temporal and transcriptional information can illuminate gene function. Together, this comprehensive delineation of mammalian cell differentiation trajectories in vivo represents a baseline for understanding the effects of gene mutations during development, as well as a roadmap for the optimization of in vitro differentiation protocols for regenerative medicine.

PMID:
30787436
DOI:
10.1038/s41586-019-0933-9

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