Single-cell transcriptomics uncovers the differentiation of a subset of murine esophageal progenitors into taste buds in vivo

Mouse esophagus is lined with a stratified epithelium, which is maintained by the constant renewal of unipotent progenitors. In this study, we profiled mouse esophagus by single-cell RNA sequencing and found taste buds specifically in the cervical segment of the esophagus. These taste buds have the same cellular composition as the ones from the tongue but express fewer taste receptor types. State-of-the-art transcriptional regulatory network analysis allowed the identification of specific transcription factors associated to the differentiation of immature progenitors into the three different taste bud cell types. Lineage tracing experiments revealed that esophageal taste buds arise from squamous bipotent progenitor, thus demonstrating that all esophageal progenitors are not unipotent. Our cell resolution characterization of cervical esophagus epithelium will enable a better understanding of esophageal progenitor potency and insights into the mechanisms involved in the development of taste buds.