Tutorial: interrogating biology using organoid technologies

Organoids provide a versatile platform for studying fundamental biology, complementing traditional cell culture and in vivo models. Their unique features, such as self-organization and the possibility for their precise manipulation, have enabled key discoveries in tissue homeostasis, development and disease. This tutorial presents an overview of organoid technologies and protocols across a broad spectrum of applications, from investigating cell fate decisions and cell-cell or cell-microbe interactions to the study of genetic diseases, species evolution and translational/clinical questions. By focusing on adult stem cell-derived intestinal and human pluripotent stem cell-derived brain organoids, we highlight models with distinct characteristics that together reflect the broader spectrum of organoid systems, tissue types and research contexts. For applications not supported by these models, we discuss organoids derived from other tissues. We also outline current challenges in the field and highlight emerging innovations that are promising to shape future directions.