Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete...

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Genomics

Background:

• Mouse extended pluripotent stem (EPS) cells show promise for in vitro embryo modeling.
• Limited extraembryonic trophoblast development capacity of EPS cells restricts whole embryo model construction, especially post-implantation embryoids.

Purpose of the Study:

• To establish a protocol for generating trophectoderm-like cells from mouse EPS cells.
• To develop a robust method for creating transgene-free post-implantation embryoids using EPS cells.
• To model key developmental events of post-implantation mouse embryogenesis in vitro.

Main Methods:

• Stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells.
• Combining trophectoderm-like cells with EPS cell-derived primitive endoderm/epiblast bilineage structures.
• Single-cell transcriptomic analysis of generated embryoids.

Main Results:

• Generated trophectoderm-like cells retain specific transcriptomic features and differentiate into trophoblast lineages in vivo.
• Successfully generated post-implantation embryoids in a transgene-free manner.
• EPS-derived embryoids recapitulate key developmental events (pro-amniotic cavity, axis formation, gastrulation) and extraembryonic tissues, showing high similarity to natural E7.5 embryos.

Conclusions:

• A novel stepwise protocol enables efficient generation of trophectoderm-like cells from mouse EPS cells.
• This advancement facilitates the robust construction of transgene-free post-implantation embryoids.
• The developed platform offers a powerful tool for in vitro modeling of post-implantation mouse embryogenesis.