Approaches to benchmark and characterize in vitro human model systems.

In vitro human models, such as gastruloids and organoids, are complex three-dimensional (3D) structures often consist of cells from multiple germ layers that possess some attributes of a developing embryo or organ. To use these models to interrogate human development and organogenesis, these 3D models must accurately recapitulate aspects of their in vivo counterparts. Recent advances in single-cell technologies, including sequencing and spatial approaches, have enabled efforts to better understand and directly compare organoids with native tissues. For example, single-cell genomic efforts have created cell and organ atlases that enable benchmarking of in vitro models and can also be leveraged to gain novel biological insights that can be used to further improve in vitro models. This Spotlight discusses the state of current in vitro model systems, the efforts to create large publicly available atlases of the developing human and how these data are being used to improve organoids. Limitations and perspectives on future efforts are also discussed.