Stem-cell-based embryo models for fundamental research and translation

Abstract

Despite its importance, understanding the early phases of human development has been limited by availability of human samples. The recent emergence of stem-cell-derived embryo models, a new field aiming to use stem cells to construct in vitro models to recapitulate snapshots of the development of the mammalian conceptus, opens up exciting opportunities to promote fundamental understanding of human development and advance reproductive and regenerative medicine. This Review provides a summary of the current knowledge of early mammalian development, using mouse and human conceptuses as models, and emphasizes their similarities and critical differences. We then highlight existing embryo models that mimic different aspects of mouse and human development. We further discuss bioengineering tools used for controlling multicellular interactions and self-organization critical for the development of these models. We conclude with a discussion of the important next steps and exciting future opportunities of stem-cell-derived embryo models for fundamental discovery and translation.

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Fig. 1: Overview of mouse and human development from pre-implantation to the onset of gastrulation.
Fig. 2: Mouse and human embryonic and extraembryonic stem cells and their corresponding developmental potencies.
Fig. 3: Existing embryoids that recapitulate different stages of mouse and human development.
Fig. 4: Bioengineering tools to promote multicellular interaction and self-organization in embryoid development.

A. Yoney/E. D. Siggia (a); N. Rivron (b); Y. Zheng (c); M. Simunovic (d)

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Acknowledgements

The authors thank S. Vianello for invaluable work on illustrations and N. Rivron, A. Yoney, E.D. Siggia, M. Simunovic and Y. Zheng for microscopic images shown in Fig. 4. J.F.’s research is supported by the University of Michigan Mechanical Engineering Department, the Michigan–Cambridge Research Initiative, the University of Michigan Mcubed Fund, the National Institutes of Health (R21 NS113518 and R21 HD100931), and the National Science Foundation (CMMI 1917304 and CBET 1901718). A.W.’s work is supported by the Rice University, the Welch Foundation (C-2021), the Simons Foundation (511709), the National Institutes of Health (R01 GM126122), and the National Science Foundation (MCB-1553228). M.P.L.’s work is supported by the École Polytechnique Fédérale de Lausanne, the National Center of Competence in Research (NCCR) ‘Bio-Inspired Materials’, and the Swiss National Science Foundation Sinergia Grant (no. 3189956). The authors apologize to colleagues whose work they could not cite owing to space restrictions.

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J.F., A.W. and M.P.L. wrote the manuscript. All authors edited and approved the manuscript.

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Correspondence to Jianping Fu or Aryeh Warmflash or Matthias P. Lutolf.

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Fu, J., Warmflash, A. & Lutolf, M.P. Stem-cell-based embryo models for fundamental research and translation. Nat. Mater. (2020). https://doi.org/10.1038/s41563-020-00829-9

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