title: Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo.
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.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.
authors.forename: Eszter
authors.identifier: http://orcid.org/0000-0002-3731-5466
authors.initials: E
authors.lastname: Posfai
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Ludwig Institute for Cancer Research, Karolinska Institutet, Stockholm, Sweden.|Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Petropoulos
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.
authors.forename: Flavia Regina Oliveira
authors.initials: FRO
authors.lastname: de Barros
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Schell
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.|Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, Canada.|Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Ludwig Institute for Cancer Research, Karolinska Institutet, Stockholm, Sweden.|Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.|Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lanner
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Janet
authors.identifier: http://orcid.org/0000-0002-3731-5466
authors.initials: J
authors.lastname: Rossant
mesh_terms: D000818:Animals; D004475:Ectoderm / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D000090683:Hippo Signaling Pathway; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases
keywords: cell fate; cell plasticity; developmental biology; inner cell mass; mouse; preimplantation; stem cells; trophectoderm