A team of researchers have developed a method to generate embryo models from murine stem cells, in the hope of providing new insights into the process of embryonic development.
No matter who you are, we all start off as a single fertilised egg cell. Firstly, the egg must divide into many omnipotent daughter cells. This means that they can differentiate into any cell type, which is required to form a fully functioning human being. After around three days, the fertilised egg is known as a blastocyst – a rapidly dividing ball of cells.
A blastocyst gives rise to three stem cell lineages – trophoblast stem cells (TSCs), embryonic stem cells (ESCs) and extraembryonic endoderm (XEN) stem cells. Usually, the generation of embryo models in the lab needs all three lineages. However, this is incredibly time-consuming as it requires complex stem cell cultures and all lineages must be kept separate.
Genetically modified embryonic stem cells
Clearly, there is a need for a more efficient method of generating embryo models. In an attempt to achieve this, a team from the University of Bonn generated an embryo-like complex, known as an embryoid, from mouse ESCs alone.
ESCs are pluripotent, rather than omnipotent. This means that whilst they can develop into multiple cell types, there are some that they cannot differentiate into. However, the researchers wanted to discover if genetically manipulating ESCs would allow for the formation of an embryoid.
“In addition to the actual embryo, the membrane that surrounds it and parts of the placenta also emerge from the egg,” senior author Professor Dr Hubert Schorle said. “Embryonic stem cells, on the other hand, cannot form these tissue structures outside the embryo.”
Formation of embryo models
Firstly, the team used genetic modification to reprogram ESCs into TSCs and XEN cells. They diverted from current procedures and decided to co-culture the three ESC lines in a 3D agarose environment. They subsequently found that the cells were able to form sophisticated embryo-like structures. Amazingly, the cells were able to self-organise themselves into these structures, suggesting that crosstalk signalling occurs between the cells.
“[The structures] resembled a 5-day-old mouse embryo,” said co-author Arik Horne. “The disordered mixture of the three cell types had therefore evolved into a strictly ordered structure, much like the one that normally emerges from a fertilised egg.”
In addition, the team analysed the genetic activity of the cells within the embryoid to confirm their findings. The results proved that the cells expressed the same genes as the cells in a natural mouse embryo, suggesting the co-culture was allowing for proper development.
Future work
For the first time, embryoids have been generated from one sole starting cell population in a 3D co-culture. The method developed in this study eliminates the need for multiple expensive cell culture reagents. It is also much faster than previous techniques used to develop embryo models. Generating models using this new method will allow scientists to forge a much deeper understanding of embryonic development.
In the future, the team aims to create embryoids from monkey ESCs. They hope that these embryoids could be used for toxicity testing to see if drugs cause any side effects in the womb. If successful, this could greatly reduce current reliance on animal testing for such experiments.
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