The Organoid Cell Atlas

To the Editor — Human organoids hold tremendous potential for biomedical applications 1 , 2 , 3 (Fig. 1a,b ). These three-dimensional structures of cultured cells recapitulate important aspects of in vivo organ development and biological function. They provide tractable in vitro models of human physiology and pathology, thereby enabling interventional studies that are difficult or impossible to conduct in human subjects. For example, organoids allow genetic and pharmacological manipulation in a complex cellular context that reflects human biology, and they enable investigations of the early stages of organ development and disease onset. Human organoids complement (and may eventually replace) animal models in many areas of preclinical drug development. Moreover, they provide patient-specific ‘avatars’ for drug development and precision therapies, including treatments for cancer, rare genetic diseases (such as cystic fibrosis) and complex multifactorial disorders (such as epilepsy). Finally, they promise to contribute to regenerative medicine, with the goal of producing functional biological structures that can be transplanted into patients. Fig. 1: Combining organoids and single-cell technology for biomedical discovery and regenerative therapy. a , Organoids can be derived from adult stem cells, which are already committed to a specific cell lineage, tissue and/or organ, or from pluripotent cells, which can give rise to a broad set of cell types but requires more complex differentiation protocols. b , Human organoids are broadly useful for in vitro modeling of biological functions, drug testing and regenerative medicine. c , Key challenges for advancing organoid research include characterization and validation of organoids, development of new organoid protocols, and applications of organoids in basic biology and biomedical research. d , Single-cell technologies promise to advance organoid research by enabling systematic validation of the derived organoids, by informing organoid protocol development, and by providing a high-resolution readout for functional perturbation experiments in human organoids. Full size image