Generation of the Nonintegrated Human Bilaminar Embryo Model (Bilaminoid) from Naïve Pluripotent Stem Cells

Human embryogenesis has been problematic to study due to technical and ethical issues. Recently, a human embryo model generated from pluripotent stem cells (PSCs) to mimic human embryogenesis, which has attracted attention as an invaluable tool for studying human embryonic development.We have successfully developed a method to efficiently induce the differentiation of naïve human PSCs, which correspond to preimplantation epiblasts, into extraembryonic cells of the blastocyst. Furthermore, by combining these cells, we developed a novel nonintegrated human embryo model called "bilaminoid" that reproduces development from preimplantation to peri-gastrulation stages. Here, we describe a detailed protocol for the bilaminoid formation.