Publication
Transgene directed induction of a stem cell-derived human embryo model
Publisher:
Cold Spring Harbor Laboratory
Date:
15-06-2023
DOI:
10.1101/2023.06.15.545082
Abstract: The human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo . Stem cell-derived models of the embryo are important tools to interrogate developmental events and tissue-tissue crosstalk during these stages 1 . Here, we establish a human post-implantation embryo model comprised of embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cells generated by transcription factor overexpression with wildtype embryonic stem cells and promote their self-organization into structures that mimic aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by hypoblast-and trophoblast-like tissues. We demonstrate that these inducible human embryoids robustly generate several cell types, including amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP signaling. This model also allowed us to identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells 2 . Modulation of the subpopulations in the hypoblast-like compartment demonstrated that extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, we present a modular, tractable, integrated 3 model of the human embryo that will allow us to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail.