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

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 Ho, Wolf Reik, Shankar Srinivas, Benjamin D. Simons, Jennifer Nichols, John C. Marioni () and Berthold Göttgens ()
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Blanca Pijuan-Sala: University of Cambridge
Jonathan A. Griffiths: University of Cambridge
Carolina Guibentif: University of Cambridge
Tom W. Hiscock: University of Cambridge
Wajid Jawaid: University of Cambridge
Fernando J. Calero-Nieto: 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
Shankar Srinivas: University of Oxford
Benjamin D. Simons: University of Cambridge
Jennifer Nichols: University of Cambridge
John C. Marioni: University of Cambridge
Berthold Göttgens: University of Cambridge

Nature, 2019, vol. 566, issue 7745, 490-495

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-0933-9

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