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Department of Physiology, Development and Neuroscience

 

Congratulations to the Zernicka-Goetz lab, who can now share their human embryo-like model, published in Nature

Knowledge of the morphogenetic transformations undergone by a human embryo following its implantation into the uterus, is limited by the inability to observe the embryo in vivo. Stem cell-derived models of the embryo are important tools to interrogate developmental events and tissue-tissue crosstalk during these stages. To solve this, the Zernicka-Goetz lab an organised three-dimensional structure derived from pluripotent stem cells that replicate some developmental processes that occur in early human embryos. This will allow researchers to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail.

“Our human embryo-like model, created entirely from human stem cells, gives us access to the developing structure at a stage that is normally hidden from us due to the implantation of the tiny embryo into the mother’s womb,” said Professor Magdalena Zernicka-Goetz,  who led the work. She added: “This exciting development allows us to manipulate genes to understand their developmental roles in a model system. This will let us test the function of specific factors, which is difficult to do in the natural embryo.”

Until now, the potential to understand the causes of human birth defects and diseases could only be observed in animal models, using cells from zebrafish and mice, for example. Legal restrictions in the UK currently prevent the culture of natural human embryos in the lab beyond day 14 of development: this time limit was set to correspond to the stage where the embryo can no longer form a twin. Scientists have only been able to study this period of human development using donated human embryos. This advance could reduce the need for donated human embryos in research.

Professor Zernicka-Goetz, who led the work, says the while these models can mimic aspects of the development of human embryos, they cannot and will not develop to the equivalent of postnatal stage humans. 

In 2021 and then in 2022 the lab announced in Developmental Cell, Nature and Cell Stem Cell journals that they had finally created model embryos from mouse stem cells that can develop to form a brain-like structure, a beating heart, and the foundations of all other organs of the body. The new models derived from human stem cells do not have a brain or beating heart, but they include cells that would typically go on to form the embryo, placenta and yolk sac, and develop to form the precursors of germ cells (that will form sperm and eggs).

There are clear regulations governing stem cell-based models of human embryos and all researchers doing embryo modelling work must first be approved by ethics committees. Journals require proof of this ethics review before they accept scientific papers for publication. The Zernicka-Goetz lab holds these approvals.