Reconstruction of functional olfactory sensory tissue from embryonic nasal stem cells

Summary During the development of the olfactory epithelium (OE), olfactory sensory neurons (OSNs) express only one member of the odorant receptor (OR) gene family, and OSNs expressing the same OR converge their axons to the same set of glomeruli on the olfactory bulb (OB). The resulting odor maps allow mice to discriminate more than 100,000 different odorants using about 1,000 ORs. It remains elusive how odor maps are formed. Here, we show a means of forming OE organoids with pseudostratified structure from mouse embryonic OE stem cells. Single-cell RNA sequencing revealed that the OE organoids give rise to all the OE cellular lineages and undergo active neurogenesis. We also found that most OSNs in OE organoids exclusively express only one type of ORs and exhibit a unique molecular code of axon guidance-related genes that can discriminate between OR classes. Thus, OE organoids could be a useful model for studying olfactory nervous system development.