Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development.

Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure.

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Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests M.Z.-G. is an advisory board member of Cell Stem Cell. M.Z.-G. and G.A. wish to declare the filing of a patent on May 5(th), 2022 by Caltech and the University of Cambridge on the “Generation of synthetic embryos from multiple stem cell types.” The patent was filed under the following numbers: CIT File No.: CIT-8826-P and Serial Number: 63/344,251.