Establishment of a novel pluripotent human stem cell of gastruloid potential

Human embryonic development is a complicated process. Fertilized oocytes create tissues and organs through cell division, proliferation, and specialization during embryogenesis, resulting in a highly complex individual. Embryonic development during the first three weeks following conception is a crucial phase of human embryogenesis, particularly from the preimplantation to the gastrula stages. At this stage, cells undergo specialization of the lineage, reorganization, and formation of embryonic organs with embryonic morphologies. Due to technical and ethical constraints as well as the restricted quantity of samples, current research on human early embryonic development is mostly unbalanced, and there are still many unexplored areas to be discovered. Here, we describe a novel type of human gastruloid pluripotent stem cells (hGPSCs) with the three germ layer differentiation potentials acquired by stimulating the differentiation of hPSCs. hGPSCs were transplanted into the testicular tubules of nude mice to replicate Carnechian stage 5 post-implantation embryonic development, beginning with gastrula-like embryo formation and culminating in organogenesis. Combining single-cell sequencing and morphological profiling, the objective of this study was to create a road map for human developmental cell lineage incorporating spatio-temporal trajectory information on post-implantation embryos and organogenesis.