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Association of TGFβ signaling with the maintenance of a quiescent stem cell niche in human oral mucosa

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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.

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Acknowledgments

We would like to thank and acknowledge the support by the Translational Pathology Shared Resource (TPSR) at Vanderbilt Medical center, which is supported by the Cancer Center Support Grant 5P30 CA068485. We also would like to thank Dr. Lloyd King from the Division of Dermatology at Vanderbilt University for providing psoriasis tissue samples. We also thank Dr. Katie Colegrove at the College of Veterinary Medicine, University of Illinois at Urbana-Champaign for providing dolphin and sea lion tissue sections for analysis.

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  1. Burnett School of Biological Sciences, University of Central Florida, Orlando, FL, 32816, USA

    Claudia D. Andl, Grégoire F. Le Bras & Thomas Andl

  2. Departments of Surgery and Cancer Biology, Vanderbilt Medical Center, Nashville, TN, 37232, USA

    Holli Loomans

  3. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Annette S. Kim

  4. James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA

    Linli Zhou & Yuhang Zhang

  5. University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826, USA

    Thomas Andl

  6. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267, USA

    Yuhang Zhang

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Andl, C.D., Le Bras, G.F., Loomans, H. et al. Association of TGFβ signaling with the maintenance of a quiescent stem cell niche in human oral mucosa. Histochem Cell Biol 146, 539–555 (2016). https://doi.org/10.1007/s00418-016-1473-0

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