Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells.
Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.
Department of Stem Cell Pathology.
Hiroko
H
Hisha
Toshihiro
T
Tanaka
Shohei
S
Kanno
Yoko
Y
Tokuyama
Yoshihiro
Y
Komai
Shuichi
S
Ohe
Hirotsugu
H
Yanai
Taichi
T
Omachi
Hiroo
H
Ueno
D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004848:Epithelium / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009940:Organoids / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D014059:Tongue / Q000166:cytology / Q000378:metabolism / Q000502:physiology
C489421:Bmi1 protein, mouse; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1