Open AccessNotch Signaling Regulates Lgr5 + Olfactory Epithelium Progenitor/Stem Cell Turnover and Mediates Recovery of Lesioned Olfactory Epithelium in Mouse Model
Author(s) -
Dai Qi,
Duan Chen,
Ren Wenwen,
Li Fangqi,
Zheng Qian,
Wang Li,
Li Wenyan,
Lu Xiaoling,
Ni Wenli,
Zhang Yanping,
Chen Yan,
Wen Tieqiao,
Yu Yiqun,
Yu Hongmeng
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2837
Subject(s) - biology , microbiology and biotechnology , progenitor cell , stem cell , lgr5 , olfactory epithelium , notch signaling pathway , cellular differentiation , olfactory mucosa , neurogenesis , signal transduction , olfactory system , cancer stem cell , neuroscience , genetics , gene
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