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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

*Korrespondierende/r Autor/-in für diese Arbeit

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.

OriginalspracheEnglisch
ZeitschriftNature
Jahrgang566
Ausgabenummer7745
Seiten (von - bis)496-502
Seitenumfang7
ISSN0028-0836
DOIs
PublikationsstatusVeröffentlicht - 28.02.2019

Fördermittel

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

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

  1. SDG 3 – Gesundheit und Wohlergehen
    SDG 3 – Gesundheit und Wohlergehen
  2. SDG 10 – Weniger Ungleichheiten
    SDG 10 – Weniger Ungleichheiten

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  • Nicht-kodierende Mutationen bei humanen Erkrankungen

    Spielmann, M. (Projektleiter*in (PI)) & Shendure, J. (Supervisor)

    01.01.1631.12.18

    Projekt: DFG EinzelprojekteDFG-Stipendien: Research Fellowships

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