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

## TL;DR

Researchers developed a method to generate mouse embryoids that mimic post-implantation development, including gastrulation, using extended pluripotent stem cells and trophectoderm-like cells.

## Contribution

A novel protocol for generating post-implantation embryoids from EPS cells by inducing trophectoderm-like cells, enabling robust in vitro embryogenesis.

## Key findings

- EPS-derived embryoids recapitulate key developmental events like pro-amniotic cavity formation, axis specification, and gastrulation.
- Single-cell transcriptomics showed high similarity between EPS-derived embryoids and natural mouse embryos at E7.5.
- Trophectoderm-like cells retain trophectoderm-specific features and differentiate into trophoblast lineages in vivo.

## Abstract

Mouse extended pluripotent stem (EPS) cells have demonstrated significant potential for generating embryo models in vitro. However, their limited capacity for extraembryonic trophoblast development has hindered their use in constructing whole embryo models, particularly post-implantation embryoids. Here, we establish a stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells. These cells retain trophectoderm-specific transcriptomic features and can differentiate into trophoblast lineages in vivo. Moreover, combining these trophectoderm-like cells with EPS cell-derived primitive endoderm/epiblast bilineage structures enabled the robust generation of post-implantation embryoids in a transgene-free manner. EPS-derived embryoids recapitulate key developmental events of post-implantation mouse embryos, including the formation of the pro-amniotic cavity, anterior-posterior axis, primitive streak, gastrulation, and complex extraembryonic tissues. Notably, single-cell transcriptomic analysis revealed a high degree of transcriptional similarity between EPS-derived embryoids at day 6 and natural E7.5 mouse embryos. Our study presents a novel platform for modeling post-implantation mouse embryogenesis in vitro.