GREAT: 3D GASTRULOID CULTURES TO MODEL NORMAL AND PATHOGENIC HUMAN DEVELOPMENT

Gastrulation is a crucial event in early human development during which the multi-layered organism begins to take form. Proper understanding of this process in humans is essential for predicting and preventing developmental disorders as well as for identifying factors that might affect adult health and longevity. Research on human gastrulation is complicated by a lack of tractable study material. This event occurs before awareness of pregnancy: even at 5-6 weeks of gestation when the very earliest abortion material is available for research gastrulation is long over. Current Dutch laws on embryo use for research prohibits their culture beyond 14 days and at that time point, gastrulation has not yet started. GREAT aims to transform the understanding of human development to benefit human health and disease by developing an advanced in vitro, 3D human gastruloid model from hiPSC. Partners here recently took major steps towards developing human gastruloids with hESCs, but advanced processes such as somitogenesis do not yet occur in this system. GREAT will advance the gastruloid system with hESCs and hiPSCs to (a) generate a comprehensive map of early human development, and (b) uncover new causes and solutions to abnormal organ formation resulting from genetic disorders, specifically regarding development of the early heart, skeletal muscle, and hematopoietic stem cells. In parallel, we will (c) assess the ethical issues arising from these embryonic models to ensure that the model that can be used responsibly in research.