Unravelling early cell fate decisions during human preimplantation development

The lineage segregation events during early embryonic development are coordinated by the dynamics of extracellular signals. They assure the correct specification of the inner cell mass (ICM), giving rise to the embryo proper, and the primitive endoderm (PrE), contributing to extra-embryonic tissues, in the epiblast (Epi). Despite the great importance of the Epi/PrE lineage segregation during early embryonic development, the lack of suitable in vitro models and human embryonic material hampered the understanding of its regulation in humans. In this project, pivotal signalling-associated transcription factors for early development will be blocked, stimulated and knocked-out by signalling modulation and the CRISPR/Cas9 technology in both human oocytes and naïve embryonic stem cells. This could allow us to characterise molecular networks involved in human Epi/PrE cell lineage commitment, with a specific focus on the role of Wnt/β-catenin, for which preliminary indications are obtained. These results might provide new model systems for in vitro human extraembryonic cell modelling to clarify how extraembryonic lineages coordinate embryo development and how defects in these lineages might contribute to pregnancy failure, hence the great interest for the field of reproductive medicine.