An aggregation of human embryonic and trophoblast stem cells reveals the role of trophectoderm on epiblast differentiation.

The interactions between extra-embryonic tissues and embryonic tissues are crucial to ensure proper early embryo development. However, the understanding of the crosstalk between the embryonic tissues and extra-embryonic tissues is lacking, mainly due to ethical restrictions, difficulties in obtaining natural human embryos, and lack of appropriate in vitro models. Here by aggregating human embryonic stem cells (hESCs) with human trophoblast stem cells (hTSCs), we revealed the hESCs robustly self-organized into a unique asymmetric structure which the primitive streak (PS) like cells exclusively distributed at the distal end to the TS-compartment, and morphologically flattened cells, presumed to be the extra-embryonic mesoderm cells (EXMC) like cells, were induced at the proximal end to hTSCs. Our study revealed two potential roles of extra-embryonic trophectoderm in regulating the proper PS formation during gastrulation and EXMCs induction from the human epiblast.