Unravelling early cell fate decisions during human preimplantation development

The dynamics of extracellular signals coordinate cell lineage
decisions during early embryo development. The correct specification
of the Inner Cell Mass in Epiblast (Epi), giving rise to the fetus, and
Primitive Endoderm (PrE) cells, contributing to the extra-embryonic
tissues, is essential ensure proper development. Even though the
Epi/PrE lineage segregation during early human development is of
great importance, its regulation remains understudied due to a lack of
suitable in vitro models and human embryo material. In this project,
we will block, stimulate, and knock-out pivotal signaling associated
transcription factors for early development by the CRISPR/Cas9
technology in both human oocytes and naive stem cells, to
characterize molecular networks involved in human Epi/PrE cell
lineage commitment, with a specific focus on the role of Wnt/ßcatenin,
for which we have obtained preliminary indications. Our
results might provide new model systems for in vitro human
extraembryonic cell modeling to clarify how extraembryonic lineages
coordinate embryo development and how defects in these lineages
might contribute to pregnancy failure, which is of great interest for the
field of reproductive medicine.