Human embryoids: A new strategy of recreating the first steps of embryonic development in vitro

Molecular mechanisms surrounding early human embryonic events such as blastocyst formation, implantation, and the specification of the body axes are some of the most attractive research questions of developmental biology today. A knowledge on the detailed signaling landscape underlying these critical events in the human could impact the way we treat early pregnancy disorders and infertility, and considerably advance our abilities to make precise human tissues in a lab. However, owing to ethical, technical, and policy restrictions, research on early human embryo development historically stalled behind animal models. The rapid progress in 3D culture of human embryonic stem cells over the past years created an opportunity to overcome this critical challenge. We review recently developed strategies of making 3D models of the human embryo built from embryonic stem cells, which we refer to as embryoids. We focus on models aimed at reconstituting the 3D epithelial characteristics of the early human embryo, namely the intra/extraembryonic signaling crosstalk, tissue polarity, and embryonic cavities. We identify distinct classes of embryoids based on whether they explicitly include extraembryonic tissues and we argue for the merit of compromising on certain aspects of embryo mimicry in balancing the experimental feasibility with ethical considerations. Human embryoids open gates toward a new field of syn-thetic human embryology, allowing to study the long inaccessible stages of early human development at un-precedented detail.

Automated summary

The molecular mechanisms of early human embryonic events have become a major focus of developmental biology research, as they have the potential to impact the treatment of pregnancy disorders and infertility. Recent progress in 3D culture of human embryonic stem cells has provided a new opportunity to study these critical events. In this review, we discuss the development of 3D models of the human embryo, known as embryoids, and their potential in studying various aspects of early human development.