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

TLDR

In vitro models derived solely from embryonic stem cells have been developed to recapitulate mouse embryogenesis, yet they fail to capture interactions between embryonic and extraembryonic tissues. The authors aim to create an ESC‑based in vitro model that reconstitutes both embryonic and extraembryonic lineages of the post‑implantation embryo. They achieve this by transcription‑factor‑mediated induction of pluripotent ESCs and the two extraembryonic lineages. The resulting model recapitulates developmental events from embryonic day 5.5 to 8.5—including gastrulation, axis formation, brain, beating heart, and extraembryonic tissues—and shows extraordinary ESC plasticity to self‑organize into a whole‑embryo‑like structure.

Abstract

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.