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


Type
Article
Change log
Authors
Lau, Kasey YC 
Rubinstein, Hernan 
Gantner, Carlos W 
Hadas, Ron 
Amadei, Gianluca 
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.

Description
Keywords
embryoid, embryogensis, in vitro model, gastrulation, neurulation, heart development, mouse embryonic stem cell, Animals, Embryo, Mammalian, Embryonic Development, Embryonic Stem Cells, Mice, Mouse Embryonic Stem Cells, Neurulation
Journal Title
Cell Stem Cell
Conference Name
Journal ISSN
1934-5909
1875-9777
Volume Title
Publisher
Elsevier BV
Sponsorship
European Research Council (669198)
Wellcome Trust (207415/Z/17/Z)