Researchers from the University of Cambridge and Caltech have created model mouse embryos from stem cells, which have beating hearts, as well as the foundations for a brain and all of the other organs in the mouse body
The results could help researchers understand why some embryos fail while others develop into a fetus as part of a healthy pregnant woman. The results could be used to develop synthetic human organs.
The research was done in the lab of a Caltech professor. In Cambridge's Department of Physiology, Development and Neuroscience, Zernicka-Goetz is a professor. The breakthrough is described in a paper in the journal Nature.
No eggs or sperm were used to develop the embryo model. The stem cells were guided to the point where they start interacting by mimicking natural processes in the lab. The researchers were able to get the stem cells to communicate by inducing the expression of a particular set of genes.
The stem cells self-organized into structures that progressed through the successive stages until the synthetic embryos had beating hearts and the foundations for a brain. This is the most advanced stage of development so far.
The ability to create the entire brain, in particular the anterior region, is a major advancement in this study.
Zernicka-Goetz says that this opens new possibilities to study the mechanisms of brain development. The proof of this principle is shown in the paper when we knock out a gene that is essential for brain and eye development. In the absence of this gene, the synthetic embryos show the defects in brain development that are present in an animal that carries thismutation. We can begin to apply this approach to genes with unknown function in the brain.
She says that the mouse embryo model develops a brain, a beating heart, and all the components that make up the body. We've got this far, it's unbelievable. This has been the goal of our community for a long time, and the focus of our work for a decade, and finally we have accomplished it.
There needs to be a dialogue between the tissues that will become the embryo and the tissues that will connect it to the mother. One of the three types of stem cells will eventually become the tissues of the body in the first week after fertilization. The extraembryonic stem cells will become the placenta and connect the fetus to the mother and provide oxygen and nutrition. The yolk sac is where the embryo grows and is where it gets its nutrition.
Stem cells send signals to each other when they start to send mechanical and chemical signals to the embryo.
Zernicka-Goetz says that the early period is the foundation for everything else in a pregnant woman's life. The pregnant woman will fail if it goes wrong.
Over the past decade, Zernicka-Goetz's team has studied these early stages of pregnancy to understand why some pregnancies fail and some succeed.
The stem cell embryo model is important because it gives us access to the developing structure at a stage that is normally hidden from us. We can manipulate genes to understand their roles in an experimental system.
To guide the development of their synthetic embryo, the researchers put together cultured stem cells representing each of the three types of tissue and allowed them to develop in proportions and an environment that would allow them to communicate with each other.
The extraembryonic cells signal to embryonic cells through chemical signals but also mechanistically, or through touch, guiding the embryo's development.
"To be able to see how it happens in a dish, to have access to these individual stem cells, to understand why so many pregnancies fail and how we might be able to prevent that from happening is quite special." We showed how the different types of stem cells communicate and how it can go wrong.
While the current research was carried out in mouse models, the researchers are developing an analogous model for human embryo development to understand mechanisms behind crucial processes that would be otherwise impossible to study.
These methods could be used to guide the development of synthetic organs for patients waiting for transplants if they are successful with human stem cells. There are a lot of people waiting for an organ transplant. The knowledge coming out of our work could be used to grow synthetic human organs to save lives. We should be able to affect and heal adult organs by using the knowledge we have on how they are made.
A paper titled "Stem cell-derived mouse embryos form anterior brain regions and a beating heart" was published. The University of Cambridge has a co-first author.
More information: Magdalena Zernicka-Goetz, Synthetic embryos complete gastrulation to neurulation and organogenesis, Nature (2022). DOI: 10.1038/s41586-022-05246-3. www.nature.com/articles/s41586-022-05246-3 Journal information: Nature
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