title: Identification of stem cells that maintain and regenerate lingual keratinized epithelial cells.
abstract: Lingual keratinized epithelial cells, which constitute the filiform papillae of the tongue, have one of the most rapid tissue turnover rates in the mammalian body and are thought to be the source of squamous cell carcinoma of the tongue. However, the mechanism of tissue maintenance and regeneration is largely unknown for these cells. Here, we show that stem cells positive for Bmi1, keratin 14 and keratin 5 are present in the base but not at the very bottom of the interpapillary pit (observed most frequently in the second or third layer (position +2 or +3) from the basal cells). Using a multicolour lineage tracing method, we demonstrated that one stem cell per interpapillary pit survives long-term. The cells were shown to be unipotent stem cells for keratinized epithelial cells but not for taste bud cells, and were found to usually be in a slow-growing or resting state; however, on irradiation-induced injury, the cells rapidly entered the cell cycle and regenerated tongue epithelium. The elimination of Bmi1-positive stem cells significantly suppressed the regeneration. Taken together, these results suggest that the stem cells identified in this study are important for tissue maintenance and regeneration of the lingual epithelium.
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata-shi, Osaka 573-1010, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tokuyama
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yanai
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohe
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation; D002470:Cell Survival; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D020287:In Situ Nick-End Labeling; D053547:Keratin-14 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D013629:Tamoxifen / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors; D014059:Tongue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; C489421:Bmi1 protein, mouse; D053547:Keratin-14; D019394:Ki-67 Antigen; C507446:Krt14 protein, mouse; D011518:Proto-Oncogene Proteins; D013629:Tamoxifen; D063150:Polycomb Repressive Complex 1
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