July 23, 2018

expert reaction to study trying to achieve gastrulation in artificial mouse embryo-like structure created from mouse stem cells

A new study, published in Nature Cell Biology, highlights how scientists – using mouse stem cells – have managed to produce artificial embryo-like structures of ‘gastrulation’.

Dr Dusko Ilic, Reader in Stem Cell Science, King’s College London, said:

“Mastermind of modelling the earliest stages of development in vitro, Magdalena Zernicka-Goetz, is again pushing the limits of what is scientifically possible.  In this outstanding piece of bioengineering design, a team from Cambridge has utilised the remarkable self-organising ability of mouse stem cells in a dish in the lab, to create multi-layered mouse embryo-like structures that could allow us to investigate molecular pathways of spatio-temporal events at the very beginning of life.”

Dr Christophe Galichet, Senior Laboratory Research Scientist, The Francis Crick Institute, said:

“‘When the sperm meets the egg’; it might sound trivial but this event starts a cascade of phenomena leading to the formation of an embryo. Once the sperm has entered the egg, the single cell starts to divide and a ball of cells is formed. Cells within the ball organise themselves into three distinct cell types: one gives rise to the embryo while the two others support the developing embryo by giving rise to the placenta (the interface between the embryo and the mum) and the yolk sac.  Stem cells do exist for these three cell types and previously the same group, as have written this new paper, had placed together embryonic and ‘placenta’ stem cells. Whilst the two cell types co-operated, they failed to fully undergo a crucial event in early life: the gastrulation, which is the formation of the three layers that form the embryo: the ectoderm (which would go on to form the skin and brain), mesoderm (which would form muscles, gonads, red blood cells, etc.) and endoderm (which would form the gastrointestinal tract, respiratory tract, etc.).

“In this new paper, the authors have combined the three types of early mouse stem cells (’embryonic’, ‘placenta’, and ‘yolk sac’).  When combined in the correct conditions (in a gel-like support) and number (correct density), the cells organise themselves in the petri dish (in this case an inverted pyramid dish). A few days after self-organisation, a few aggregates showed embryonic structure and developed in what would resemble natural mouse embryos. In this paper, the authors have characterised extensively and thoroughly the development of the self-assembled mouse embryos they called ETX embryos.  They analysed whether the ETX embryos behaved the same as natural embryos and, amazingly, they do. Furthermore, the mouse ETX embryos seemed to fully undergo gastrulation, a crucial event in early life. The authors have bypassed the ‘sperm meets the egg’ requirement in the formation of an early mouse embryo.  However, it will be important to analyse whether these self-organised embryos are able to form term animals by implementing them to surrogate female mice.

“Understanding human early embryo development is not as trivial as with the mouse.  Indeed, work on early human embryos is highly and tightly regulated.  Furthermore, early human embryos used for research purposes are very rare.  While the paper did not use human stem cells, it is not too far-fetched to think the technique could one day be applied to studying early human embryos, though this has not been done yet.  Indeed, the three early human stem cell types (embryonic, ‘placenta’ and ‘yolk sac’) are readily available and it is possible that the method described in the paper could in future be used as a non ‘sperm meets the egg’ way of generating human embryos for research.  These self-assembled human embryos would be an invaluable tools to understand early human development as well as understanding when things go wrong, but we are not there yet.  Furthermore, ethical discussions would need to assess the status of these self-organised embryos if the method described in this paper did work with human stem cells.”

* ‘Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo structures’ by Berna Sozen et al. published in Nature Cell Biology on Monday 23 July 2018.

Declared interests

Dr Dusko Ilic: “I declare no conflict of interest.”

Dr Christophe Galichet: “I do not have any interest in this study.”