Modelling late gastrulation in stem cell-derived monkey embryo models.

Abstract

Stem cell-derived embryo models could greatly facilitate our understanding of embryonic development. Although human and monkey embryo models have reached early gastrulation stage^1-7, the development of robust models beyond this time remains to be accomplished⁸. Here, using an optimized 3D suspension culture system, we have successfully advanced the in vitro culture of a stem cell-derived monkey blastoid to day 25. Morphological and histological analyses showed that these monkey embryoids underwent gastrulation and largely recapitulated key developmental events of the late gastrulation stage observed in vivo, with the appearance of a neural plate, haematopoietic system, allantois, primitive gut, primordial germ cells, yolk sac structures and progenitors of other organs, excluding trophoblast derivatives. Single-cell transcriptomic analyses revealed that the lineage composition and differentiation trajectories of cells in these monkey embryoids were similar to those found in natural embryos during gastrulation. Thus, this primate stem cell-derived embryo model provides a valuable platform for dissecting the mechanisms of primate embryonic development from blastocyst to late gastrulation stage.