O-156 Embryo-like models: Using 3D gastruloids to understand human development

Abstract

Abstract The mammalian embryo develops through coordinated cell fate decisions that enable emerging spatiotemporal and morphogenetic complexity. While much insight into this process has been gained through studying model organisms, including mouse embryos, equivalent experiments are technically and ethically challenging in the human embryonic context. Instead, we use gastruloids: 3-dimensional aggregates of pluripotent stem cells that undergo multilineage differentiation to all three germ layers, polarise their gene expression and exhibit axial organisation that recapitulates many of the features of gastrulation and early organogenesis. By closely examining the dynamics and coordination of cell fate decisions and spatial gene expression organisation, we hope to better understand the regulatory logic behind early developmental events, particularly those that are human-specific. Likewise, by carefully manipulating the environment in which these gastruloids are grown, we can bias the structures towards particular lineages and morphological structures of interest. Doing so allows us to explore many of the principles of early development, and provides an opportunity to probe the mechanisms of biomedically-relevant conditions, such as congenital abnormalities.