This is the first instance of a research group using stem cells to make advanced embryos, Hanna told the Times of Israel. “Our next challenge is to understand how stem cells know what to do – how they self-assemble into organs and find their way to their assigned spots inside an embryo.”
Apart from helping reduce the use of animals in stem cell research, the techniques developed in his lab could one day also help become a reliable source of cells, tissues, and organs for transplantation.
The findings of the study were published in the journal Cell.
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extra-embryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating-like structures with embryonic and extra-embryonic compartments, remains unknown. Here we adapt a recently established platform for prolonged ex utero growth of natural embryos, to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, starting from naïve ESCs. This was achieved by co-aggregating non-transduced ESCs, with naïve ESCs transiently expressing Cdx2- and Gata4- to promote their priming towards trophectoderm and primitive endoderm lineages, respectively. sEmbryosly adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extra-embryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naïve pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.