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, Berthold Göttgens*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)490-495
Number of pages6
JournalNature
Volume566
Issue number7745
Early online date20 Feb 2019
DOIs
Publication statusPublished - 28 Feb 2019

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    Pijuan-Sala, B., Griffiths, J. A., Guibentif, C., Hiscock, T. W., Jawaid, W., Calero-Nieto, F. J., Mulas, C., Ibarra-Soria, X., Tyser, R. C. V., Ho, D. L. L., Reik, W., Srinivas, S., Simons, B. D., Nichols, J., Marioni, J. C., & Göttgens, B. (2019). A single-cell molecular map of mouse gastrulation and early organogenesis. Nature, 566(7745), 490-495. https://doi.org/10.1038/s41586-019-0933-9