Modeling Post-Implantation Human Development to Yolk Sac Blood Emergence

Implantation of the human embryo commences a critical developmental stage that comprises profound events including axis formation, gastrulation, and the 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. Stem cell models of human embryo have emerged to help unlock the mysteries of this stage. Here, we present a model of early post-implantation human embryogenesis (embryoid) with an extra-embryonic endoderm and mesoderm niche to support early hematopoiesis. This human embryo model is genetically inducible, and its unanticipated self-organization results in the development of the amniotic cavity, formation of bilaminar disc embryonic morphology, an anterior hypoblast pole and posterior domain. The extra-embryonic layer of iDiscoid presents multilineage yolk sac tissue morphogenesis with extra-embryonic mesoderm and lacks trophoblast. Its development captures distinct waves of yolk sac hematopoiesis including the emergence of erythroid, myeloid and lymphoid cells . iDiscoid offers an easy-to-use, high-throughput, reproducible, and scalable platform to probe multifaceted aspects of human development and blood formation at early post-implantation stage. It will provide a tractable human-based model for drug testing, disease modeling, and a unique cell source for regenerative medicine. To investigate the cell types that develop from this model system over time, we conducted scRNAseq on this model at a number of different ages for the purposes of identifying cell development and comparing the transcriptomes to existing human embryo data.