title: Wnt-responsive Lgr5⁺ globose basal cells function as multipotent olfactory epithelium progenitor cells.
abstract: Persistent neurogenesis in the olfactory epithelium provides a unique model to study neural stem cell self-renewal and fate determination. In the olfactory neuroepithelium, globose basal cells (GBCs) are considered to be the direct progenitors of olfactory neurons. However, the study of neurogenesis from GBCs has been impeded by the paucity of GBC-specific markers. Here we report that Lgr5, a recently discovered adult stem cell marker, is exclusively expressed in GBCs in neonatal and adult mice. Lgr5(+) cells display characteristics of cycling stem cells, including Ki67 expression and EdU incorporation. Lineage tracing analysis demonstrates that Lgr5(+) GBCs regenerate multiple cell types under normal turnover condition or after olfactory lesion. Furthermore, upregulation or downregulation of Wnt signaling in vivo indicates a key role of Wnt signaling not only in maintaining Lgr5(+) cell proliferation and promoting neuroregeneration, but also in delaying sensory neuron maturation. Together, our observations provided new insights into the dynamics of neurogenesis in the olfactory epithelium.
authors.affiliation: Department of Microbiology and Molecular Genetics and.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Molecular Genetics and Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Shenghe
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery and.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
authors.affiliation: Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Randall R
authors.initials: RR
authors.lastname: Reed
authors.affiliation: Department of Microbiology and Molecular Genetics and Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and liuh4@pitt.edu.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016667:Bacterial Capsules / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D005434:Flow Cytometry; D019922:GAP-43 Protein / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000502:physiology*; D051842:Olfactory Marker Protein / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D018799:Intercellular Adhesion Molecule-1; D019394:Ki-67 Antigen; D051842:Olfactory Marker Protein; D043562:Receptors, G-Protein-Coupled; D001616:beta-Galactosidase; C499317:Ascl1 protein, mouse; C493597:Lgr5 protein, mouse; C501008:Neurod1 protein, mouse; C497598:Omp protein, mouse; C039514:capsular polysaccharide K14; C485184:enhanced green fluorescent protein
keywords: Lgr5; Wnt; globose basal cells; neural stem cells; olfactory epithelium; regeneration