Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Synthetic Embryology

Background:

• In vitro cultured stem cells can contribute to embryonic and extraembryonic tissues.
• The ability of cultured stem cells to independently form entire gastrulating embryo-like structures is unknown.

Purpose of the Study:

• To determine if cultured stem cells can generate complete gastrulating embryo-like structures with both embryonic and extraembryonic compartments.
• To model mammalian embryonic development beyond gastrulation using synthetic embryo models.

Main Methods:

• Adaptation of an ex utero growth platform for natural embryos.
• Co-aggregation of naive embryonic stem cells (ESCs) with ESCs transiently expressing Cdx2 or Gata4.
• Generation of mouse post-gastrulation synthetic whole embryo models (sEmbryos) from ESCs.

Main Results:

• sEmbryos successfully underwent gastrulation and advanced through key developmental milestones.
• Developed organ progenitors within complex extraembryonic compartments, resembling E8.5 mouse embryos.
• Demonstrated functional reconstitution and modeling of the entire mammalian embryo beyond gastrulation.

Conclusions:

• Naive pluripotent cells possess significant plasticity to self-organize into complex structures.
• Synthetic embryo models can recapitulate critical stages of mammalian post-gastrulation development.
• This study provides a novel platform for studying early mammalian embryogenesis.