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Cambridge Stem Cell Institute

 

 

Dr Thorsten Boroviak

 

Primate Embryogenesis

Departmental affiliation: 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. After completion of his master’s thesis in 2007, he was awarded a PhD-fellowship at the University of Sheffield to work on neuronal differentiation of mouse embryonic stem cells. Thorsten early postdoctoral work in the laboratories of Prof. Austin Smith and Prof. Jennifer Nichols provided transcriptional and functional evidence that the closest in vivo counterpart of mouse embryonic stem cells is the preimplantation epiblast. Between 2012 and 2015, 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 signaling during early lineage specification. In 2017, Thorsten was awarded a Sir Henry Dale Fellowship to start his own group – the Laboratory for Primate Embryogenesis – at the Department of Physiology, Development and Neuroscience at the University of Cambridge. Thorsten is a member of the Cambridge Stem Cell Institute, the Centre for Trophoblast Research, the Anne McLaren Trust Fund and Fellow of Darwin College.

 

Research

The Boroviak lab focuses on how embryonic cells organise themselves to form the most complex lifeforms, such as human and non-human primates.

They follow primate embryonic cells through parts of their journey to provide insights into human development. Their approaches include simultaneous genetic and epigenetic high-throughput sequencing from single cells, embryonic stem cell culture and bioengineering of stem cell-based embryo models.

A deeper understanding of primate development is vital for innovative treatments of implantation failure, infertility and cancer as well as clinical applications of stem cell biology.

 

Embryo implantation, gastrulation and organogenesis

The first signs of the human body axis can be traced back to the second week of gestation. To get to this point, the blastocyst implants and establishes a small sheet of cells, the embryonic disc. Deeply embedded within extraembryonic tissues, the embryo undergoes a reorganization process termed “gastrulation”, which transforms the embryonic disc into three germ layers and determines the entire future body plan.

Most of our knowledge on mammalian gastrulation is based on mouse, but human embryogenesis differs in anatomical architecture, timing, molecular configuration and sequence of cell-fate decisions. For instance, in human and non-human primates, the implanting epiblast polarises into a rosette, gives rise to amnion and forms a flat EmDisc. Rodent embryos form amnion later in development, after gastrulation.

 

Research goals

The central aim of our research focuses on delineating the molecular crosstalk between the human embryonic disc and extraembryonic signalling centres, which control the sequence of cell-fate allocation in the primitive streak. To understand how these signalling centres emerge, we need to elucidate how extraembryonic lineages are specified in primate postimplantation development.

 

Boroviak research

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

 

Our lab was the first to reveal the molecular landscape in primate embryos between implantation and gastrulation in vivo (Bergmann et al., Nature 2022). We developed epiblast- and amnion-spheroid cultures using microfluidics (Schindler et al., Stem Cell Reports 2021; Munger et al., Development 2022) and pioneered computational approaches, including spatial-identity-mapping, to determine the identity of in vitro cultured cells. Our ongoing work involves micropatterning, blastoids, microfluidics and bioprinting to emulate human and non-human primate development in stem cell-based embryo models.

Boroviak research 2

Epiblast-like marmoset embryonic stem cells

 

 

The results from our work will be critical to understand human implantation failure, how errors in gastrulation can lead to congenital malformations and how germ layers are patterned for organ formation.

 

Spatial transcriptome profiling of primate embryos view the video

 

Publications: 

The Boroviak Group

Boroviak Group Members: 

Yuxi Ding
Thomas Tan

Collaborators

Prof. Erika Sasaki (Central Institute for Experimental Animals, Tokyo, Japan)

Prof. Ruediger Behr (German Primate Centre, Germany)

Prof. Jan Brosens (University of Warwick, UK)

Prof. Florian Hollfelder (Department of Biochemistry, Cambridge, UK)

Prof. Kathy Niakan (Centre for Trophoblast Research, Cambridge, UK)

Dr. Peter Rugg Gunn (Babraham Institute, Cambridge, UK)

Prof. Wolf Reik (Altos Labs, Cambridge, UK)