title: Label-retaining, quiescent globose basal cells are found in the olfactory epithelium.
abstract: The vertebrate olfactory epithelium (OE) is known for its ability to renew itself throughout life as well as to reconstitute after injury. Although this remarkable capacity demonstrates the persistence of stem cells and multipotent progenitor cells, their nature in the OE remains undefined and controversial, as both horizontal basal cells (HBCs) and globose basal cells (GBCs) have features in common with each other and with stem cells in other tissues. Here, we investigate whether some among the population of GBCs satisfy a key feature of stem cells, i.e., mitotic quiescence with retention of thymidine analogue label and activation by injury. Accordingly, we demonstrate that some GBCs express p27(Kip1) , a member of the Kip/Cip family of cyclin-dependent kinase inhibitors. In addition, some GBCs retain bromodeoxyuridine or ethynyldeoxyuridine for an extended period when the pulse is administered in neonates followed by a 1-month chase. Their identity as GBCs was confirmed by electron microscopy. All spared GBCs express Ki-67 in the methyl bromide (MeBr)-lesioned OE initially after lesion, indicating that the label-retaining (LR) GBCs are activated in response to injury. LR-GBCs reappear during the acute recovery period following MeBr exposure, as demonstrated with 2- or 4-week chase periods after labeling. Taken together, our data demonstrate the existence of LR-GBCs that are seemingly activated in response to epithelial injury and then re-established after the initial phase of recovery is completed. In this regard, some among the GBCs satisfy a common criterion for functioning like stem cells.
authors.affiliation: Department of Developmental, Molecular, and Chemical Biology, School of Medicine, Tufts University, Boston, Massachusetts, 02111.
authors.forename: Woochan
authors.initials: W
authors.lastname: Jang
authors.forename: Xueyan
authors.initials: X
authors.lastname: Chen
authors.forename: Daniel
authors.initials: D
authors.lastname: Flis
authors.forename: Margaret
authors.initials: M
authors.lastname: Harris
authors.forename: James E
authors.initials: JE
authors.lastname: Schwob
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D053555:Keratin-5 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009676:Noxae / Q000633:toxicity; D009831:Olfactory Mucosa / Q000166:cytology* / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000145:classification* / Q000378:metabolism* / Q000648:ultrastructure; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D006842:Hydrocarbons, Brominated; D053555:Keratin-5; D019394:Ki-67 Antigen; D019006:Neural Cell Adhesion Molecules; D009676:Noxae; C488416:Tubb3 protein, rat; D014404:Tubulin; D050760:Cyclin-Dependent Kinase Inhibitor p27; C005218:methyl bromide; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D001973:Bromodeoxyuridine; D013936:Thymidine
keywords: label-retaining cells; mitotic quiescence; neuronal progenitors; tissue stem cells