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

Author

Listed:
  • Blanca Pijuan-Sala

    (University of Cambridge
    University of Cambridge)

  • Jonathan A. Griffiths

    (University of Cambridge)

  • Carolina Guibentif

    (University of Cambridge
    University of Cambridge)

  • Tom W. Hiscock

    (University of Cambridge
    University of Cambridge)

  • Wajid Jawaid

    (University of Cambridge
    University of Cambridge)

  • Fernando J. Calero-Nieto

    (University of Cambridge
    University of Cambridge)

  • Carla Mulas

    (University of Cambridge)

  • Ximena Ibarra-Soria

    (University of Cambridge)

  • Richard C. V. Tyser

    (University of Oxford)

  • Debbie Lee Lian Ho

    (University of Cambridge)

  • Wolf Reik

    (Babraham Institute
    University of Cambridge
    Wellcome Genome Campus)

  • Shankar Srinivas

    (University of Oxford)

  • Benjamin D. Simons

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Jennifer Nichols

    (University of Cambridge)

  • John C. Marioni

    (University of Cambridge
    Wellcome Genome Campus
    Wellcome Genome Campus)

  • Berthold Göttgens

    (University of Cambridge
    University of Cambridge)

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.

Suggested Citation

  • Blanca Pijuan-Sala & Jonathan A. Griffiths & Carolina Guibentif & Tom W. Hiscock & Wajid Jawaid & Fernando J. Calero-Nieto & Carla Mulas & Ximena Ibarra-Soria & Richard C. V. Tyser & Debbie Lee Lian H, 2019. "A single-cell molecular map of mouse gastrulation and early organogenesis," Nature, Nature, vol. 566(7745), pages 490-495, February.
    • Handle: RePEc:nat:nature:v:566:y:2019:i:7745:d:10.1038_s41586-019-0933-9
    DOI: 10.1038/s41586-019-0933-9
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