Organoid Modeling of Mouse Anterior Tongue Epithelium Reveals Regional and Cellular Identities

Abstract The tongue is essential for swallowing, taste perception, and mechanosensation. The anterior and posterior parts of the tongue have region‐specific developmental origins and are maintained by adult epithelial stem/progenitor cells. In vitro models that can be used to investigate anterior tongue biology have been lacking. Here, a protocol is developed to generate a long‐term expanding organoid model from the adult mouse dorsal anterior tongue. Anterior tongue organoids consist of Lgr6 + cells, Sox2 + stem/progenitor cells, and Hoxc13 + filiform papillae progenitor cells. Furthermore, anterior tongue organoids share region‐specific transcriptomic profiles, gene regulatory networks, and signaling pathways with anterior tongue tissue. Anterior tongue organoids can be differentiated into various epithelial cell types, including Merkel‐like cells, keratinocytes, and taste bud cells. Gene regulatory network analysis reveals transcriptional programs associated with Krt8 + cell and Krt23+/Sbsn+ keratinocyte differentiation in the organoids. Together, this study provides an in vitro model of mouse dorsal tongue epithelium.