title: A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification.
abstract: The esophageal epithelium is a prototypical stratified squamous epithelium that exhibits an exquisite equilibrium between proliferation and differentiation. After basal cells proliferate, they migrate outward toward the luminal surface, undergo differentiation, and eventually slough due to apoptosis. The identification and characterization of stem cells responsible for the maintenance of the esophageal epithelium remains elusive. Here, we employed Hoechst dye extrusion and BrdU label-retaining assays to identify in mice a potential esophageal stem cell population that localizes to the basal cell compartment. The self-renewing capacity of this population was characterized using a clonogenic assay and a 3D organotypic culture model. The putative esophageal stem cells were also capable of epithelial reconstitution in vivo in direct esophageal epithelial injury models. In both the 3D organotypic culture and direct mucosal injury models, the putative stem cells gave rise to undifferentiated and differentiated cells. These studies therefore provide a basis for understanding the regenerative capacity and biology of the esophageal epithelium when it is faced with injurious insults.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kalabis
authors.forename: Kenji
authors.initials: K
authors.lastname: Oyama
authors.forename: Takaomi
authors.initials: T
authors.lastname: Okawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Carmen Z
authors.initials: CZ
authors.lastname: Michaylira
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Stairs
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
authors.forename: J Alan
authors.initials: JA
authors.lastname: Diehl
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D004935:Esophageal Diseases / Q000378:metabolism; D004947:Esophagus / Q000166:cytology* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D001973:Bromodeoxyuridine