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Symposium Leatures


Single Cell Analysis of Cell Commitment in the Preimplantation Mouse Embryo


Plenary Lecture

Single Cell Analysis of Cell Commitment in the Preimplantation Mouse Embryo

Professor Janet Rossant, Hospital for Sick Children, University of Toronto, Canada


The formation of the mouse blastocyst involves the gradual segregation of the outer trophectoderm (TE) from the enclosed inner cell mass (ICM). Position-dependent Hippo signaling in the inner cells of the developing embryo is required to block Cdx2 expression and promote inner cell mass formation. However, the exact timing of commitment of the two lineages and how this relates to the timing of active Hippo signaling is still unclear. Using a Cdx2-eGFP fusion reporter line, we undertook RNAseq analysis of single cells during the process of lineage segregation. We were able to correlate progressive shifts in overall gene expression profiles with segregation of Cdx2 high versus low cells. The trophectoderm profile was stabilized earlier than the ICM profile. We undertook a series of experimental tests of lineage specification and commitment of cells sorted by Cdx2-eGFP expression and found that the inner cells of the embryo retain the ability to regenerate outer TE over a longer time window than the TE retains ICM capacity. This window of plasticity of ICM cells is governed by their responsiveness to Hippo signaling. Final commitment to ICM fate may be governed by activation of the Jak-Stat signaling pathway at the blastocyst stage. These and studies from other groups are continuing to provide new insights into the complex dynamics of lineage specification in the blastocyst.


Biography of Professor Janet Rossant, CC, PhD, FRS, FRSC

Professor Janet Rossant

Janet Rossant, CC, PhD, FRS, FRSC is Senior Scientist and Chief of Research Emeritus at the Hospital for Sick Children in Toronto and President and Scientific Director of the Gairdner Foundation. She is an internationally recognized developmental and stem cell biologist, exploring the origins of stem cells in the early embryo and their applications to understanding and treating human disease. She led the research institute at the Hospital for Sick Children from 2005 to 2015. She has received many honours and recognition for her work, including four honorary degrees, and election to the Royal Societies of London and Canada, and the National Academy of Sciences, USA.