Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb:84:102134.
doi: 10.1016/j.gde.2023.102134. Epub 2023 Dec 5.

Topical section: embryonic models (2023) for Current Opinion in Genetics & Development

Charlotte E Handford  1 , Sergi Junyent  2 , Victoria Jorgensen  3 , Magdalena Zernicka-Goetz  4
Affiliations
Review

Topical section: embryonic models (2023) for Current Opinion in Genetics & Development

Charlotte E Handford et al. Curr Opin Genet Dev. 2024 Feb.

Abstract

Stem cell-based mammalian embryo models facilitate the discovery of developmental mechanisms because they are more amenable to genetic and epigenetic perturbations than natural embryos. Here, we highlight exciting recent advances that have yielded a plethora of models of embryonic development. Imperfections in these models highlight gaps in our current understanding and outline future research directions, ushering in an exciting new era for embryology.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors are inventors on the following patents: 1. Patent applicant: Caltech. Inventors: Magdalena Zernicka-Goetz, Berna Sozen, and Victoria Jorgensen. Application number: 17/692,790. Specific aspect of the paper covered in patent application: Reconstructing human early embryogenesis in vitro with pluripotent stem cells. 2. Patent applicant: Caltech and Cambridge Enterprise Limited. Inventors: Magdalena Zernicka-Goetz, Gianluca Amadei, and Charlotte Handford. Application number: 63/397,630. Specific aspect of the paper covered in patent application: Synthetic embryos. 3. Patent Applicant: Caltech and Cambridge Enterprise Limited. Inventors: Magdalena Zernicka-Goetz, Bailey Weatherbee, and Carlos Gantner. Application number: 63/403,684. Specific aspect of the paper covered in patent application: Stem cell-derived model of the human embryo.

Figures

Figure 1.
Figure 1.. Current models of in vitro totipotency in mouse and human cells.
Schematic representation of the strategies followed to capture in vitro totipotency in mouse (A) and human (B) cells. Gray boxes indicate totipotency hallmarks displayed by in vitro totipotent cells.
Figure 2.
Figure 2.. Mouse and human embryo morphogenesis.
Schematic representation of the morphogenetic transformations of mouse (top) and human (bottom) embryos before or shortly after implantation. Key differences between the models include the morphology of the embryo at the onset of gastrulation: in the embryonic day (E)6.5, the mouse embryo is organized in an ‘egg cylinder’ morphology, while the E14 human embryo presents as a flat embryonic disk overlayed by the amniotic cavity and the amnion, and underlaid by the hypoblast and the yolk sac.
Figure 3.
Figure 3.. Three dimensional stem cell-based embryo models.
Schematic representation of the current three-dimensional stem cell-based models of mouse and human embryo development.
See this image and copyright information in PMC

References

    1. Ai Z, Niu B, Yin Y, Xiang L, Shi G, Duan K, Wang S, Hu Y, Zhang C, Zhang C, Rong L, Kong R, Chen T, Guo Y, Liu W, Li N, Zhao S, Zhu X, Mai X, … Li T. (2023). Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids. BioRxiv, 2023.06.15.545180.

      **This paper described the formation of a human peri-implantation embryo model of the epiblast and hypoblast that forms a bilaminar disk structure surrounded by extraembryonic mesenchyme-like cells.

    1. Amadei G, Handford CE, Qiu C, De Jonghe J, Greenfeld H, Tran M, Martin BK, Chen D-Y, Aguilera-Castrejon A, Hanna JH, Elowitz MB, Hollfelder F, Shendure J, Glover DM, & Zernicka-Goetz M. (2022). Embryo model completes gastrulation to neurulation and organogenesis. Nature, 610(7930), 143–153.

      **This paper described the development of ETiX-embryos comprised of ESC and TSCs to stages of early organogenesis (E8.5).

    1. Amadei G, Lau KYC, De Jonghe J, Gantner CW, Sozen B, Chan C, Zhu M, Kyprianou C, Hollfelder F, & Zernicka-Goetz M. (2021). Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro. Developmental Cell, 56(3), 366–382.e9. - PMC - PubMed

    1. Bao M, Cornwall-Scoones J, Sanchez-Vasquez E, Chen DY, De Jonghe J, Shadkhoo S, Hollfelder F, Thomson M, Glover DM, & Zernicka-Goetz M. (2022). Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension. Nature Cell Biology 2022 24:9, 24(9), 1341–1349.

      *This paper described the role of the “cadherin code” and cortical stiffness as drivers of cell-cell sorting in the ETX model.

    1. Beccari L, Moris N, Girgin M, Turner DA, Baillie-Johnson P, Cossy AC, Lutolf MP, Duboule D, & Arias AM (2018). Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids. Nature, 562(7726), 272–276. - PubMed

Publication types

LinkOut - more resources