Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

Elife. 2017 Feb 22:6: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.

Keywords: cell fate; cell plasticity; developmental biology; inner cell mass; mouse; preimplantation; stem cells; trophectoderm.

MeSH terms

  • Animals
  • Ectoderm / embryology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Hippo Signaling Pathway
  • Mice
  • Protein Serine-Threonine Kinases / metabolism*
  • Sequence Analysis, RNA
  • Signal Transduction*

Substances

  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Protein Serine-Threonine Kinases

Grants and funding

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