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The Notch signaling pathway regulates stem cell proliferation and differentiation in multiple tissues and organs, and is required for tissue maintenance. However, the role of Notch in regulation of olfactory epithelium (OE) progenitor/stem cells to maintain tissue function is still not clear. A recent study reported that leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 ( Lgr5 ) is expressed in globose basal cells (GBCs) localized in OE. Through lineage tracing in vivo, we found that  Lgr5  +  cells act as progenitor/stem cells in OE. The generation of daughter cells from Lgr5 +  progenitor/stem cells is delicately regulated by the Notch signaling pathway, which not only controls the proliferation of  Lgr5  +  cells and their immediate progenies but also affects their subsequent terminal differentiation. In conditionally cultured OE organoids in vitro, inhibition of Notch signaling promotes neuronal differentiation. Besides, OE lesion through methimazole administration in mice induces generation of more  Notch1  +  cells in the horizontal basal cell (HBC) layer, and organoids derived from lesioned OE possesses more proliferative  Notch1  +  HBCs. In summary, we concluded that  Notch  signaling regulates  Lgr5  +  GBCs by controlling cellular proliferation and differentiation as well as maintaining epithelial cell homeostasis in normal OE. Meanwhile,  Notch1  also marks HBCs in lesioned OE and  Notch1  +  HBCs are transiently present in OE after injury. This implies that  Notch1  +  cells in OE may have dual roles, functioning as GBCs in early development of OE and HBCs in restoring the lesioned OE. S tem  C ells   2018;36:1259–1272

stem cells

Notch Signaling Regulates Lgr5 +  Olfactory Epithelium Progenitor/Stem Cell Turnover and Mediates Recovery of Lesioned Olfactory Epithelium in Mouse Model