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

• Published in: eLife Vol. 6
• Main Authors: Posfai, Eszter, Petropoulos, Sophie, de Barros, Flavia Regina Oliveira, Schell, John Paul, Jurisica, Igor, Sandberg, Rickard, Lanner, Fredrik, Rossant, Janet
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 22.02.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Binding sites; Blastomeres; CDX2 protein; cell fate; cell plasticity; Cellular signal transduction; Developmental Biology and Stem Cells; Divisions; Ectoderm - embryology; Embryonic development; Experiments; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genes, Reporter; Green Fluorescent Proteins - analysis; Green Fluorescent Proteins - genetics; inner cell mass; Medical research; Medicin och hälsovetenskap; Mice; Observations; Plasticity; preimplantation; Protein-Serine-Threonine Kinases - metabolism; Ribonucleic acid; RNA; Sequence Analysis, RNA; Signal Transduction; Statistical analysis; Transcription; Transcription factors; Trophectoderm; mouse; stem cells; trophectoderm; cell fate; developmental biology; inner cell mass; cell plasticity; preimplantation
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.22906

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.