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

TLDR

Spatially ordered embryo‑like structures self‑assembled from blastocyst‑derived stem cells can be generated to mimic embryogenesis in vitro, but their assembly system and developmental potential require further study. The study aims to develop a nonadherent suspension‑shaking system that co‑cultures embryonic, trophoblast, and extra‑embryonic endoderm stem cells to form embryo‑like structures (ETX‑embryoids). The authors employ this nonadherent suspension‑shaking culture to allow the three cell types to self‑assemble into lineage‑specific compartments, producing ETX‑embryoids. The resulting ETX‑embryoids exhibit lineage‑specific sorting, molecular and morphogenic events resembling wild‑type embryos—including lumenogenesis, asymmetric expression of mesoderm and primordial germ cell markers, anterior visceral endoderm‑like tissues—and efficiently initiate implantation with decidual tissue formation when transplanted into pseudopregnant mice, underscoring their value as a model for embryogenesis.

Abstract

Abstract 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.