Modeling Post-Implantation Human Development to Yolk Sac Blood Emergence

Implantation of the human embryo commences a critical developmental stage that comprises profound morphogenetic alteration of embryonic and extra-embryonic tissues, axis formation, gastrulation, and emergence of yolk sac hematopoietic system. Our mechanistic knowledge of this window of human life remains limited due to restricted access to in vivo samples for both technical and ethical reasons. Here, we present iDiscoid, a model of early post-implantation human embryogenesis, produced from induced pluripotent stem cells. iDiscoids capture reciprocal co-development of embryonic tissue and extra-embryonic endoderm and mesoderm niche. The morphogenesis of iDiscoids exhibit unanticipated self-organization and tissue boundary formation that results in the development of the amniotic cavity, formation of bilaminar disc embryonic morphology, and acquisition of an anterior hypoblast pole and posterior domain. The extra-embryonic layer of iDiscoids demonstrates multilineage yolk sac tissue specification with extra-embryonic mesoderm and captures different waves of early hematopoiesis. iDiscoids offer an easy-to-use, high-throughput, reproducible, and scalable platform to probe multifaceted aspects of human development at its early post-implantation stage. As such it can provide a tractable model for drug testing, developmental toxicology, and disease modeling in a human context.