Position- and Hippo signaling-dependent plasticityduring lineage segregation in the early mouse embryo
- Hospital for Sick Children, Canada
- Karolinska Institutet, Sweden
- University Health Network, Canada
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.
Data availability
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Sequential loss of plasticity during trophectoderm and inner cell mass lineage segregation in the mouse embryoPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE84892).
Article and author information
Author details
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.
Reviewing Editor
- Robb Krumlauf, Stowers Institute for Medical Research, United States
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.
Version history
- Received: November 2, 2016
- Accepted: February 13, 2017
- Accepted Manuscript published: February 22, 2017 (version 1)
- Version of Record published: March 28, 2017 (version 2)
- 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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Position- and Hippo signaling-dependent plasticityduring lineage segregation in the early mouse embryo
eLife 6:e22906.
https://doi.org/10.7554/eLife.22906
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