Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Nat Commun. 2014 Jun 30;5:4226. doi: 10.1038/ncomms5226.

Abstract

NANOG is a pluripotency transcription factor in embryonic stem cells; however, its role in adult tissues remains largely unexplored. Here we show that mouse NANOG is selectively expressed in stratified epithelia, most notably in the oesophagus where the Nanog promoter is hypomethylated. Interestingly, inducible ubiquitous overexpression of NANOG in mice causes hyperplasia selectively in the oesophagus, in association with increased cell proliferation. NANOG transcriptionally activates the mitotic programme, including Aurora A kinase (Aurka), in stratified epithelia, and endogenous NANOG directly binds to the Aurka promoter in primary keratinocytes. Interestingly, overexpression of Nanog or Aurka in mice increased proliferation and aneuploidy in the oesophageal basal epithelium. Finally, inactivation of NANOG in cell lines from oesophageal or head and neck squamous cell carcinomas (ESCCs or HNSCCs, respectively) results in lower levels of AURKA and decreased proliferation, and NANOG and AURKA expression are positively correlated in HNSCCs. Together, these results indicate that NANOG has a lineage-restricted mitogenic function in stratified epithelia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Proliferation
  • Epithelium / enzymology
  • Epithelium / metabolism*
  • Esophagus / metabolism
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitosis
  • Nanog Homeobox Protein
  • Promoter Regions, Genetic
  • Species Specificity

Substances

  • Homeodomain Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Aurka protein, mouse
  • Aurora Kinase A

Associated data

  • GEO/GSE48370