An international team of scientists led by the Centre for Excellence in Brain Science and Intelligence Technology from Chinese Academy of Sciences (CAS) in Shanghai (PR of China) and the Pompeu Fabra University report in Nature the development of the first stem cell model of primate gastrulation in the lab. The model developed with monkey pluripotent stem cells is first assembled into a blastoid and then undergoes gastrulation, generating the seeds for the different organs and tissues in the body. While the use of this model involves a lower ethical burden compared to human models—because it is made from non human primate cells—it could be a proxy for the origin of human disease and, significantly, the effects of the environment and drugs on the development of the embryo. 

Lewis Wolpert once quipped that the most important moment of your life is not marriage, birth or death but gastrulation. This is the process that turns the mass of cells that results from the fertilization of an egg into the outline of an organism; the first glimpse of what will become an organism. In humans the process is initiated on day 14 from the start of development and, due to its happening deep in the womb, remains inaccessible to observation and experimentation. The reasons are not only the difficulty to access the embryos at these early stages, but also ethical and regulatory barriers that prevent growing human embryos in the lab beyond day 14. Nevertheless, this is a critical moment in the construction of tissues and organs and medical studies suggest that many pathologies have their origin in the mechanisms that underlie this process.

Today, the laboratory of Zhen Liu at CAS in collaboration with Alfonso Martinez Arias at the Department of Medicine and Life Sciences at UPF report in Nature a model of primate gastrulation organized in the lab from monkey pluripotent stem cells. They first assembled the cells into a blastoid –a cellular structure made in the lab that mimics the organization of the blastocyst– which then transitioned into a structure that mimics the epiblast –the cellular substrate for gastrulation. Over the course of a week, the structure underwent gastrulation, generating the seeds for the different organs and tissues with reference to a coordinate system that emerges with the process.

‘There are meticulous descriptions of gastrulation in monkey embryos that, by comparison, ensure that our model accurately reflects what happens in the embryo,’ explains Zhen Liu of the CAS. ‘We wanted to be sure we had a reliable model. Something unusual when working with embryo replicas based on stem cells,’ adds Alfonso Martinez Arias of UPF. 

Tracing the origin of diseases

As the model is made with monkey cells –where the ethical burden is lower than with human cells–, the authors were also able to make mutations in developmental genes and assess their consequences for body plan formation. Making, for the first time, an experimental manipulation in a primate embryo model. ‘With our model, we demonstrated that mutants associated with some already described diseases can be introduced and analysed, as well as study the effects of drugs on embryo development’, states Liu.  

According to Martinez-Arias, ‘Multiple studies in medical embryology and teratology have shown us that many diseases have their origins during gastrulation. For example, we know that some heart defects are caused by a poor specification of the primordia during gastrulation’. And adds, ‘with this model, we can now reproduce the diseases, to study them in detail and try to understand them better.’.

This work opens up the possibility of using this model as a proxy for the origin of human disease and, significantly, the effects of the environment and drugs on the development of the embryo. It also paves the way for similar studies with human cells.

About the field

Over the last ten years, Pluripotent Stem Cells have been used to create models of the earliest stages of mammalian development. These models offer a possibility to learn about the origin of normal and abnormal development. For example, blastoids mimic the organization of the blastocyst, the structure from which the embryo will develop after implantation in the uterus, and are being used to study events associated with early development and implantation in mice, monkeys and humans. Work with mouse cells has been able to recapitulate gastrulation in vitro and the emergence of the body leading to structures that, in some instances, mimic the embryo closely. These studies have raised the possibility of doing the same with human cells and this gaining access to human gastrulation. However, despite efforts from many laboratories, similar efforts with human cells have not been successful. At best, the current models reach the initial stages of gastrulation but do not progress beyond them.

Both Alfonso Martinez Arias and Zhen Liu have pioneered much of this work, and their collaboration in this study represents an important breakthrough towards the development of useful models of human development and the understanding of neonatal pathologies.

Reference article: 

Li, J., Li, J., Cao, J., Shang, S., Zhang, L., Gao, F., Fu, J., Chen, H., Cui, G., Wu, H., Wang, X., Martinez-Arias, A., Sun, Q., & Liu, Z. (2025). Modelling late gastrulation in stem cell-derived monkey embryo models. Nature. https://doi.org/10.1038/s41586-025-09831-0