Scientists engineer human embryo-like model to unlock the secrets of early development

To overcome these limitations, scientists turned to laboratory models that emulate embryos using stem cells from both mice and humans, rather than relying on eggs and sperm.

Zernicka-Goetz and her team have now taken another step forward by developing a human embryo-like model that simulates the second week of human development—after the embryo has successfully implanted in the womb.

These embryo-like models are not living entities capable of developing into fully formed embryos, but they do provide valuable insights into the intricate mechanisms of embryonic development, human defects and diseases, pregnancy failures, and even the potential for growing synthetic organs for transplantation.

"Our human embryo-like model, created entirely from pluripotent 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," explained Zernicka-Goetz, who is in the process of relocating her lab to Caltech from the University of Cambridge.

This project allows scientists to manipulate genes and explore their roles in the developmental process—an endeavor that is otherwise challenging to undertake in a natural embryo.

This is also not the first of its kind. As reported by Interesting Engineering, the Gurdon Institute at the University of Cambridge has produced a model human embryo with a heartbeat and some blood that might provide insights into the "black box" stage of life.

Zernicka-Goetz's pioneering work in developing integrated stem cell-derived embryo models has garnered recognition, as she has been named the recipient of the esteemed 2023 Ogawa-Yamanaka Stem Cell Prize.

Awarded by Gladstone Institutes and supported by Cell Press, this prize acknowledges her decade-long dedication to research in this field. Her integrated models combine embryonic and extraembryonic stem cells, representing the cells that develop into supporting structures for the growing embryo, such as the placenta and yolk sac.

Step-by-step progress

The research team has previously made significant progress in generating mouse embryo-like models from embryonic and extraembryonic stem cells. These models, published in a series of papers from 2017 to 2021, demonstrated the ability to form the progenitors of various brain regions, the spinal cord, the gut tube, and even beating hearts.

While the new human embryo-like models are not as advanced as their mouse counterparts and do not possess beating heart-like structures, they do contain both embryonic and extraembryonic tissues that would typically develop into the placenta, yolk sac, and amnionic sac.

The creation of this human embryo-like model represents a significant milestone in our quest to comprehend the complex processes underlying early human development.

Abstract

The human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage 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 stages1. Here, we establish a model of the human post-implantation embryo, a human embryoid, comprised of embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cells generated by transcription factor overexpression with wildtype embryonic stem cells and promote their self-organization into structures that mimic several aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by extraembryonic-like tissues. Our functional studies demonstrate that the epiblast-like domain robustly differentiates to amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP cues. In addition, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells2. Modulation of the subpopulations in the hypoblast-like compartment demonstrated that extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, we present a modular, tractable, integrated3 model of the human embryo that will allow us to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail.