1. Developmental Biology
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Position- and Hippo signaling-dependent plasticityduring lineage segregation in the early mouse embryo

  1. Eszter Posfai
  2. Sophie Petropoulos
  3. Flavia RO de Barros
  4. John Paul Schell
  5. Igor Jurisica
  6. Rickard Sandberg
  7. Fredrik Lanner
  8. Janet Rossant  Is a corresponding author
  1. Hospital for Sick Children, Canada
  2. Karolinska Institutet, Sweden
  3. University Health Network, Canada
Research Article
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Cite this article as: eLife 2017;6:e22906 doi: 10.7554/eLife.22906

Abstract

The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling.

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The following data sets were generated

Article and author information

Author details

  1. Eszter Posfai

    Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Sophie Petropoulos

    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Flavia RO de Barros

    Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. John Paul Schell

    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Igor Jurisica

    Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Rickard Sandberg

    Ludwig Institute for Cancer Research, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Fredrik Lanner

    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Janet Rossant

    Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
    For correspondence
    janet.rossant@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3731-5466

Funding

Canadian Institutes of Health Research (FDN-143334)

  • Janet Rossant

Ragnar Söderbergs stiftelse (M67/13)

  • Fredrik Lanner

Swedish Foundation for Strategic Research (ICA12-0001)

  • Fredrik Lanner

Knut och Alice Wallenbergs Stiftelse (2015.0096)

  • Fredrik Lanner

Swedish Research Council (2013-2570)

  • Fredrik Lanner

Restracomp fellowship (post-doctoral fellowship)

  • Eszter Posfai

Mats Sundin Fellowship (post-doctoral fellowship)

  • Sophie Petropoulos

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal work was carried out following Canadian Council on Animal Care Guidelines for Use of Animals in Research and Laboratory Animal Care under protocols (protocol number: 20-0026H) approved by The Centre for Phenogenomics Animal Care Committee.

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Publication history

  1. Received: November 2, 2016
  2. Accepted: February 13, 2017
  3. Accepted Manuscript published: February 22, 2017 (version 1)
  4. Version of Record published: March 28, 2017 (version 2)
  5. Version of Record updated: October 25, 2017 (version 3)

Copyright

© 2017, Posfai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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