Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

Sung Yoon Catherine Kang, Nagarajan Kannan, Lewei Zhang, Victor Martinez, Miriam P. Rosin, Connie J. Eaves

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.

Original languageEnglish (US)
Pages (from-to)1210-1225
Number of pages16
JournalStem Cell Reports
Volume5
Issue number6
DOIs
StatePublished - Dec 8 2015
Externally publishedYes

Keywords

  • epithelial progenitors
  • HPV
  • oropharyngeal cancer
  • tonsil

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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