Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo
Eszter Posfai,
Sophie Petropoulos,
Flavia Regina Oliveira de Barros,
John Paul Schell,
Igor Jurisica,
Rickard Sandberg,
Fredrik Lanner,
Janet Rossant
Affiliations
Eszter Posfai
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
Sophie Petropoulos
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
Flavia Regina Oliveira de Barros
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada
John Paul Schell
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden
Igor Jurisica
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
Rickard Sandberg
Ludwig Institute for Cancer Research, Karolinska Institutet, Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
Fredrik Lanner
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada
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.
