Synthetic mouse embryos develop to new key stage of life
An international team of scientists has created the most lifelike artificial embryos ever, even guiding them through "the most important event in life" – a key development stage known as gastrulation. Skipping the sperm-meets-egg chapter, the researchers combined three types of mouse stem cells into an embryo that was just about ready to be implanted into a womb.
In past research, scientists have grown egg cells out of mouse skin cells, and developed a new technique to grow large numbers of model embryos to study development and disease. The new study builds on previous work by the same team, headed up by scientists at Cambridge.
Three types of stem cells make up an embryo at a stage of development known as the blastocyst stage. The embryonic stem cells (ESCs) are the ones that will become the body itself, while the trophoblast stem cells (TSCs) go on to form the placenta, and the primitive endoderm stem cells (PESCs) become the nutrient-rich yolk sac.
Last year, the Cambridge-led team managed to create artificial embryos by combining ESCs and TSCs, with an extracellular matrix for support and to guide them into the right shape. This time, the researchers managed to incorporate the third type of stem cell – PESCs – for the first time, without which the embryo couldn't develop much further.
Specifically, they wouldn't make it to the gastrulation stage. This step is when the embryo divides itself into three layers of cells, with those layers going on to dictate which tissues or organs the cells will develop into.
"Proper gastrulation in normal development is only possible if you have all three types of stem cell," says Magdalena Zernicka-Goetz, lead researcher on the study. "In order to reconstruct this complex dance, we had to add the missing third stem cell. By replacing the jelly that we used in earlier experiments with this third type of stem cell, we were able to generate structures whose development was astonishingly successful."
Sure enough, the researchers saw their embryos reach this stage, splitting into three layers as a natural embryo would. The timing, architecture and gene activity also all went off without a hitch, following the normal pattern.
"Our artificial embryos underwent the most important event in life in the culture dish," says Zernicka-Goetz. "They are now extremely close to real embryos. To develop further, they would have to implant into the body of the mother or an artificial placenta."
As the most developed in the world, these artificial embryos should help give scientists a clearer view into early development, where it can often be visually and ethically difficult to see what's going on.
The research was published in the journal Nature Cell Biology.
Source: University of Cambridge