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Common and distinct transcriptional signatures of mammalian embryonic lethality

Author

Listed:
  • John E. Collins

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Richard J. White

    (Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

  • Nicole Staudt

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Ian M. Sealy

    (Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

  • Ian Packham

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Neha Wali

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Catherine Tudor

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Cecilia Mazzeo

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Angela Green

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Emma Siragher

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Edward Ryder

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Jacqueline K. White

    (Wellcome Sanger Institute, Wellcome Genome Campus
    The Jackson Laboratory)

  • Irene Papatheodoru

    (European Bioinformatics Institute, Wellcome Genome Campus)

  • Amy Tang

    (European Bioinformatics Institute, Wellcome Genome Campus)

  • Anja Füllgrabe

    (European Bioinformatics Institute, Wellcome Genome Campus)

  • Konstantinos Billis

    (European Bioinformatics Institute, Wellcome Genome Campus)

  • Stefan H. Geyer

    (Medical University of Vienna)

  • Wolfgang J. Weninger

    (Medical University of Vienna)

  • Antonella Galli

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Myriam Hemberger

    (The Babraham Institute, Babraham Research Campus
    University of Cambridge
    University of Calgary)

  • Derek L. Stemple

    (Wellcome Sanger Institute, Wellcome Genome Campus
    Camena Bioscience, The Science Village)

  • Elizabeth Robertson

    (University of Oxford)

  • James C. Smith

    (The Francis Crick Institute)

  • Timothy Mohun

    (The Francis Crick Institute)

  • David J. Adams

    (Wellcome Sanger Institute, Wellcome Genome Campus)

  • Elisabeth M. Busch-Nentwich

    (Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

Abstract

The Deciphering the Mechanisms of Developmental Disorders programme has analysed the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines in order to investigate the causes of embryonic lethality. Here we show that individual whole-embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) identifies transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. For example, our data suggest that Hmgxb3 is involved in DNA-damage repair and cell-cycle regulation. Further, we separate embryonic delay signatures from mutant line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during early embryogenesis (4–36 somites). Analysis of transcription outside coding sequence identifies deregulation of repetitive elements in Morc2a mutants and a gene involved in gene-specific splicing. Collectively, this work provides a large scale resource to further our understanding of early embryonic developmental disorders.

Suggested Citation

  • John E. Collins & Richard J. White & Nicole Staudt & Ian M. Sealy & Ian Packham & Neha Wali & Catherine Tudor & Cecilia Mazzeo & Angela Green & Emma Siragher & Edward Ryder & Jacqueline K. White & Ire, 2019. "Common and distinct transcriptional signatures of mammalian embryonic lethality," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10642-x
    DOI: 10.1038/s41467-019-10642-x
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    Cited by:

    1. Ninoslav Pandiloski & Vivien Horváth & Ofelia Karlsson & Symela Koutounidou & Fereshteh Dorazehi & Georgia Christoforidou & Jon Matas-Fuentes & Patricia Gerdes & Raquel Garza & Marie E. Jönsson & Anit, 2024. "DNA methylation governs the sensitivity of repeats to restriction by the HUSH-MORC2 corepressor," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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