Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells

Nat Commun. 2019 Jan 30;10(1):496. doi: 10.1038/s41467-019-08378-9.


Spatially ordered embryo-like structures self-assembled from blastocyst-derived stem cells can be generated to mimic embryogenesis in vitro. However, the assembly system and developmental potential of such structures needs to be further studied. Here, we devise a nonadherent-suspension-shaking system to generate self-assembled embryo-like structures (ETX-embryoids) using mouse embryonic, trophoblast and extra-embryonic endoderm stem cells. When cultured together, the three cell types aggregate and sort into lineage-specific compartments. Signaling among these compartments results in molecular and morphogenic events that closely mimic those observed in wild-type embryos. These ETX-embryoids exhibit lumenogenesis, asymmetric patterns of gene expression for markers of mesoderm and primordial germ cell precursors, and formation of anterior visceral endoderm-like tissues. After transplantation into the pseudopregnant mouse uterus, ETX-embryoids efficiently initiate implantation and trigger the formation of decidual tissues. The ability of the three cell types to self-assemble into an embryo-like structure in vitro provides a powerful model system for studying embryogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / cytology*
  • Embryo Implantation
  • Embryo, Mammalian / cytology*
  • Embryonic Development / genetics
  • Embryonic Development / physiology
  • Female
  • Gene Expression Regulation, Developmental
  • Germ Cells / cytology
  • Mice
  • Stem Cells / cytology*