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Dr Thorsten Boroviak

Boroviak Thorsten

 

  Dr Thorsten Boroviak

  Primate Embryogenesis

  Departmental affiliation & Laboratory Location: Department of Physiology, Development and
   Neuroscience, Centre for Trophoblast Research

Biography

Thorsten originates from Austria, where he studied Molecular Biology at the University of Vienna. During his postdoctoral research, he addressed the relationship of pluripotent embryonic stem cells to the early embryo. Thorsten provided transcriptional and functional evidence that the closest in vivo counterpart of mouse embryonic stem cells is the preimplantation epiblast. Moreover, he pioneered genome-wide comparison of mouse to non-human primate development by lineage-specific RNA-seq, which identified a primate specific role for WNT signalling during early lineage specification. In 2017, Thorsten was awarded the Sir Henry Dale Fellowship to start his laboratory at the Department of Physiology, Development and Neuroscience and became a fellow of Christ’s College at the University of Cambridge.

Boroviak research

Marmoset blastocyst stained with markers of the three lineages: epiblast, hypoblast and trophoblast.

Research

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.

Boroviak research 2

Epiblast-like marmoset embryonic stem cells.

External links

https://boroviaklab.pdn.cam.ac.uk/

https://www.pdn.cam.ac.uk/directory/thorsten-boroviak

CSCI Collaborators

Austin Smith

Jenny Nichols

Kevin Chalut