title: Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid.
abstract: Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Aihara
authors.affiliation: Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Research Center, Cincinnati, Ohio.
authors.forename: Maxime M
authors.initials: MM
authors.lastname: Mahe
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schumacher
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Matthis
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Ren
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Research Center, Cincinnati, Ohio.
authors.forename: Taeko K
authors.initials: TK
authors.lastname: Noah
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Toru
authors.initials: T
authors.lastname: Matsu-ura
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Research Center, Cincinnati, Ohio.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Moore
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Christian I
authors.initials: CI
authors.lastname: Hong
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Yana
authors.initials: Y
authors.lastname: Zavros
authors.affiliation: Division of Oral Biology, The Ohio State University, Columbus, Ohio.
authors.forename: Scott
authors.initials: S
authors.lastname: Herness
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Research Center, Cincinnati, Ohio.
authors.forename: Noah F
authors.initials: NF
authors.lastname: Shroyer
authors.affiliation: Department of Nutritional Science and Food Safety, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Iwatsuki
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania.
authors.forename: Peihua
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Research Center, Cincinnati, Ohio.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Helmrath
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Marshall H
authors.initials: MH
authors.lastname: Montrose
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D058948:Cell Tracking; D018960:Hyaluronan Receptors / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009940:Organoids / Q000166:cytology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D013650:Taste Buds / Q000166:cytology*; D046509:Tissue Culture Techniques
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled