Synthetic Morphogenesis of Human Bilaminar Disc Via Genetically Encoded Transcriptional Programs

Implantation of human embryo commences a critical developmental stage that comprises profound morphogenetic alteration of embryonic and extraembryonic tissues, axis formation and gastrulation events. Our mechanistic knowledge of this window of human life remains limited due to restricted access to natural healthy samples for both technical and ethical reasons. Here we describe a system that employs human induced pluripotent stem cells engineered with an inducible human transcription factor gene circuit to demonstrate genetically guided cell fates with single-cell transcriptional profiles similar to post-implantation embryonic and extraembryonic lineages. We show self-organization of these populations into three-dimensional multifate epiblast-like compartments surrounded by a yolk sac hypoblast layer. We observe self-organization and tissue boundary formation that recapitulates yolk sac-like tissue specification, the formation of bilaminar disc-like structure and the development of an amniotic-like cavity. This approach provides a simple platform for studying peri-implantation embryonic fate decisions and for the exploration of synthetic developmental engineering using a genetically encoded transcriptional program.