title: Association of TGFβ signaling with the maintenance of a quiescent stem cell niche in human oral mucosa.
abstract: A dogma in squamous epithelial biology is that proliferation occurs in the basal cell layer. Notable exceptions are squamous epithelia of the human oral cavity, esophagus, ectocervix, and vagina. In these human epithelia, proliferation is rare in the basal cell layer, and the vast majority of cells positive for Ki67 and other proliferation markers are found in para- and suprabasal cell layers. This unique human feature of a generally quiescent basal cell layer overlaid by highly proliferative cells offers the rare opportunity to study the molecular features of undifferentiated, quiescent, putative stem cells in their natural context. Here, we show that the quiescent human oral mucosa basal cell layer expresses putative markers of stemness, while para- and suprabasal cells are characterized by cell cycle genes. We identified a TGFβ signature in this quiescent basal cell layer. In in vitro organotypic cultures, human keratinocytes could be induced to express markers of these quiescent basal cells when TGFβ signaling is activated. The study suggests that the separation of basal cell layer and proliferation in human oral mucosa may function to accommodate high proliferation rates and the protection of a quiescent reserve stem cell pool. Psoriasis, an epidermal inflammatory hyperproliferative disease, exhibits features of a quiescent basal cell layer mimicking normal oral mucosa. Our data indicate that structural changes in the organization of epithelial proliferation could contribute to longevity and carcinogenesis.
authors.affiliation: Burnett School of Biological Sciences, University of Central Florida, Orlando, FL, 32816, USA.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Andl
authors.affiliation: Burnett School of Biological Sciences, University of Central Florida, Orlando, FL, 32816, USA.
authors.forename: Grégoire F
authors.initials: GF
authors.lastname: Le Bras
authors.affiliation: Departments of Surgery and Cancer Biology, Vanderbilt Medical Center, Nashville, TN, 37232, USA.
authors.forename: Holli
authors.initials: H
authors.lastname: Loomans
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
authors.forename: Annette S
authors.initials: AS
authors.lastname: Kim
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Linli
authors.initials: L
authors.lastname: Zhou
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA. yuhang.zhang@uc.edu.|Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267, USA. yuhang.zhang@uc.edu.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Burnett School of Biological Sciences, University of Central Florida, Orlando, FL, 32816, USA. thomas.andl@ucf.edu.|University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826, USA. thomas.andl@ucf.edu.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-5555-468X
authors.initials: T
authors.lastname: Andl
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Longevity; Psoriasis; Quiescence; Squamous epithelia; Stem cells; Transforming growth factor beta