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Thorsten Boroviak

Thorsten Boroviak

Principal Investigator, Laboratory for Primate Embryogenesis, Centre for Trophoblast Research

Sir Henry Dale Fellow


Research Interests

Full profile on the PDN website: https://www.pdn.cam.ac.uk/directory/thorsten-boroviak

 

Our goal is to bioengineer synthetic primate embryos to transform our understanding of implantation, germ cell specification and the continuum of pluripotent states in primate embryogenesis.

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.

Summary in plain English: Life originates from a single cell. The fertilised egg gives rise to the embryo, a handful of loosely attached cells. In our lab, we focus on how embryonic cells organise themselves to form the most complex lifeforms, such as human and non-human primates. We follow primate embryonic cells through parts of their journey to provide insights into human development. Our research is vital for innovative treatments of implantation failure, infertility and cancer as well as clinical applications of stem cell biology.

 

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

Research Supervision

Thorsten Boroviak, is accepting applications for PhD students.

Key Publications

Boroviak T and Nichols J, (2017), Postimplantation development predicts extraembryonic potential of naive pluripotency in primates, Development, 2017

Scognamiglio R, Cabezas-Wallscheid N, Their M, Altamura S, Reyes A, Baumgärtner D, Prendergast A, Carnevalli L, Paleske L, Boroviak T, Wörsdörfer P, Essers M, Eisenman R, Edenhofer F, Bertone P, Huber W, Hoeven F, Smith A and Trumpp A, Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause, Cell, 2016

Boroviak T*, Loos R*, Lombard P, Behr R, Sasaki E, Nichols J, Smith A and Bertone P, (2015), Lineage-specific profiling delineates the emergence and progression of naïve pluripotency in mammalian embryogenesis, Developmental Cell, 2015

Boroviak T. and Nichols J, (2015), Maximising clonal embryonic stem cell derivation by ERK pathway inhibition, Methods in Molecular Biology, 2015

Boroviak T. and Nichols J, (2014), The birth of embryonic pluripotency, Philosophical transactions of the Royal Society 2014

Boroviak T, Loos R, Bertone P, Smith A and Nichols J, The ability of inner cell mass cells to self-renew as embryonic stem cells is acquired upon epiblast specification, Nature Cell Biology 2014

Tatsumoto S, Adati N, Tohtoki Y, Sakaki Y, Boroviak T, Habu S, Okano H, Suemizu H, Sasaki E and Satake M, (2013), Development and characterization of cDNA resources for the common marmoset: one of the experimental primate models, DNA Res. 2013

Boroviak T. and Rashbass P, (2010), The Apical Polarity Determinant Crumbs 2 is a Novel Regulator of Embryonic Stem Cell Derived Neural Progenitors, Stem Cells 2010

Reitinger S, Boroviak T, Laschober GT, Fehrer C, Muellegger J, Lindner H, Lepperdinger G, (2008), High-yield recombinant expression of the extremophile enzyme, bee hyaluronidase in Pichia pastoris, Protein Expr Purif. 2008