Thorsten Edwin Boroviak PhD

The founding population of the entire foetus is established at the end of preimplantation development in the epiblast. Implantation is a landmark event where the embryo undergoes major reorganisation. In rodents, the pluripotent epiblast gives rise to a cup-shaped epithelium, the egg-cylinder. However, primate development dramatically diverges from the rodent paradigm: The primate epiblast represents a flat disc and forms an amniotic cavity, specifying extraembryonic amnion directly after implantation. This suggests substantial differences in the epiblast pluripotency network. Moreover, the recent discovery that primates specify germ cells from nascent amnion further highlights the fundamental importance of primate-specific lineage segregation events.

In our lab, we aim to illuminate the cell-fate decision of early primate development by transcriptional and epigenetic profiling of marmoset embryos, in collaboration with the leading primate centres in Germany and Japan. Marmosets represent the least sentient of primates and, importantly, their embryonic development is conserved with human. Our approach entails combined single-cell RNA-seq and bisulfite sequencing as well as comprehensive computational analysis to compile a genome-wide blueprint of primate development.

In parallel to computational approaches, we are establishing authentic embryonic stem cell lines representative of the three lineages of the primate blastocyst: epiblast, hypoblast and trophoblast. Our goal is to assemble these embryonic lineages into three dimensional structures, mimicking the embryo just before implantation. These synthetic embryos will then be plated on endometrial cells and allowed to attach. The advantages of synthetic embryos include maximal experimental flexibility and an unlimited supply for genome-wide functional screens. Modelling early primate postimplantation development in a dish will provide unprecedented insights into embryonic disc and amnion formation, with far-reaching implications for cancer and stem cell biology, germ cell development and treatments for implantation failure.

Collaborators

Erika Sasaki, Central Institute for Experimental Animals, Tokyo, Japan

Ruediger Behr, German Primate Centre, Goettingen, Germany

Wolf Reik, Babraham Institute, Cambridge 

Graham Burton, Centre for Trophoblast Research, Cambridge

Margherita Turco, Centre for Trophoblast Research, Cambridge

Jenny Nichols, Cambridge Stem Cell Institute, Cambridge

Austin Smith, Cambridge Stem Cell Institute, Cambridge

Paul Bertone, Cambridge Stem Cell Institute, Cambridge

Sabine Dietmann, Cambridge Stem Cell Institute, Cambridge