PT  - JOURNAL ARTICLE
AU  - Kasey Y.C. Lau
AU  - Hernan Rubinstein
AU  - Carlos W. Gantner
AU  - Gianluca Amadei
AU  - Yonatan Stelzer
AU  - Magdalena Zernicka-Goetz
TI  - Mouse-embryo model derived exclusively from embryonic stem cells undergo neurulation and heart development
AID  - 10.1101/2022.08.01.502371
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.01.502371
4099  - http://biorxiv.org/content/early/2022/08/02/2022.08.01.502371.short
4100  - http://biorxiv.org/content/early/2022/08/02/2022.08.01.502371.full
AB  - 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 extra-embryonic 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, and formation of the anterior-posterior axis, brain, 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 extra-ordinary plasticity of ESCs to self-organize and generate a whole embryo-like structure.Competing Interest StatementThe authors have declared no competing interest.