The single-cell transcriptional landscape of mammalian organogenesis

Junyue Cao, Malte Spielmann, Xiaojie Qiu, Xingfan Huang, Daniel M. Ibrahim, Andrew J. Hill, Fan Zhang, Stefan Mundlos, Lena Christiansen, Frank J. Steemers, Cole Trapnell*, Jay Shendure

*Corresponding author for this work

Abstract

Mammalian organogenesis is a remarkable process. Within a short timeframe, the cells of the three germ layers transform into an embryo that includes most of the major internal and external organs. Here we investigate the transcriptional dynamics of mouse organogenesis at single-cell resolution. Using single-cell combinatorial indexing, we profiled the transcriptomes of around 2 million cells derived from 61 embryos staged between 9.5 and 13.5 days of gestation, in a single experiment. The resulting ‘mouse organogenesis cell atlas’ (MOCA) provides a global view of developmental processes during this critical window. We use Monocle 3 to identify hundreds of cell types and 56 trajectories, many of which are detected only because of the depth of cellular coverage, and collectively define thousands of corresponding marker genes. We explore the dynamics of gene expression within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle.

Original languageEnglish
JournalNature
Volume566
Issue number7745
Pages (from-to)496-502
Number of pages7
ISSN0028-0836
DOIs
Publication statusPublished - 28.02.2019

Funding

Acknowledgements We thank members of the Shendure and Trapnell labs, especially D. Cusanovich, R. Daza, G. Findlay, A. McKenna, H. Pliner and V. Ramani, as well as L. McInnes, D. Beier, N. Ahituv and S. Tapscott for helpful discussions and feedback; M. Zager for major contributions to the website; R. Hunter, and R. Rualo at the Transgenic Resources Program of University of Washington and N. Brieske and A. Stiege at the Max Planck Institute for Molecular Genetics for their assistance; S. Geuer for the Fndc3a probe. M.S. was supported by a grant from the Deutsche Forschungsgemeinschaft (SP1532/3-1). This work was funded by the Paul G. Allen Frontiers Group (Allen Discovery Center grant to J.S. and C.T.), grants from the NIH

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being
  2. SDG 10 - Reduced Inequalities
    SDG 10 Reduced Inequalities

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  • Non-coding genetic variants in human disease

    Spielmann, M. (Principal Investigator (PI)) & Shendure, J. (Supervisor)

    01.01.1631.12.18

    Project: DFG Individual ProjectsDFG Scholarships: Research Fellowships

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