A post-implantation model of human embryo development includes a definitive hematopoietic niche

Stem cell-derived embryo models are crucial for investigations to advance our knowledge of early human development. Here, we present a post-gastrulation three-dimensional (3D) embryo model that is kinetically matured to promote multi-lineage organogenesis with tissues comparable to those found in Carnegie stage (CS)12-CS16 human embryos. The resulting structures include cardiomyocytes, hepatocytes, endothelial cells, and hematopoietic cells, but they lack a yolk sac. Notably, we observe SOX17⁺RUNX1⁺ hemogenic buds, where we detect the maturation of hematopoietic stem cells (HSCs). These hemogenic niches, where endothelial-to-hematopoietic transition occurs, contain instructive (DLL4, SCF) and restrictive (FGF23) factors for the maturation of HSC. These HSCs have the potential to differentiate into myeloid and lymphoid lineages, and, therefore, they are equivalent to definitive hematopoiesis. Accordingly, we call our model hematoids, which offer both a versatile tool for investigating tissue-scale mechanisms of human development and a potential source of human HSCs for mechanistic studies and cell therapies.