Illuminating cell fate decisions in the implanting primate by embryo profiling and ex vivo functional analysis

Cells in the early embryo are of particular interest as they harbour the potential to form all cell types found in the adult body. Most of our knowledge about these cells is based on mouse studies. However, early development in human and non-human primates radically diverges from the rodent paradigm. Primates even form additional placental tissues upon implantation. Despite the tremendous potential for biomedical research, the underlying mechanisms remain unknown.

I propose to investigate the primate-specific aspects of early development of the embryo after implantation, building on strong collaborations with primate centres in Germany and Japan. Gene expression analysis of marmoset embryos post-implantation using the latest next-generation sequencing techniques will identify regulators of cell-fate decisions. This can only be done in a non-human primate, because human embryos at this stage cannot be used on ethical grounds. I will subsequently assemble embryo-derived cell lines into three dimensional structures, mimicking the embryo just before implantation. These synthetic embryos are a novel approach to experimentally validating the critical regulators of primate implantation in a tissue culture dish.

This model will provide unprecedented insights into human and non-human primate development with far-reaching implications for cancer and stem cell biology, placental research and treatments for implantation failure.