Sozen, B. et al. Nat. Cell Biol. 20, 979–989 (2018).
The ability to recapitulate early mammalian embryogenesis in a culture dish would give unprecedented access to study development and disease. Although the embryo is derived from one tissue, the epiblast, it cannot develop without extraembryonic tissue interactions. The Zernicka-Goetz group previously showed that coculture of mouse embryonic stem (ES) cells with trophoblast stem (TS) cells (placenta progenitors) in extracellular matrix leads to the spontaneous generation of structures with two compartments that closely resemble natural embryos. These synthetic ‘ET’ embryos form a preamniotic cavity, but fall short of specifying mesoderm and initiating gastrulation. In their new work, Sozen et al. develop conditions for coculturing of ES and TS cells with extraembryonic endoderm (XEN) cells (yolk sac progenitors). Remarkably, even in the absence of matrix, the resulting ‘ETX’ embryos go on to specify mesoderm and a XEN-derived visceral endoderm-like tissue. ETX embryos have morphology and gene expression resembling that in the mid-gastrula stage, and highlight the dramatic self-organizing capacity of the embryo.