The pluripotency factor NANOG regulates the mitotic program of adult stratified epithelia.. Mus musculus

NANOG is a key transcription factor for pluripotency in embryonic stem cells. However, its role in adult tissues remains largely unexplored. Here, we show that mouse NANOG is expressed in the progenitor layer of stratified epithelia, including esophagus, forestomach and skin. Accordingly, the Nanog promoter is hypomethylated in the epithelial layers of the esophagus and forestomach. Interestingly, ubiquitous transgenic overexpression of NANOG in mice induces hyperplasia in stratified epithelia, but not in other tissues. Mechanistically, we show that NANOG transcriptionally activates the mitotic program selectively in stratified epithelia, and endogenous NANOG directly binds the Aurora kinase A (Aurka) promoter in keratinocytes. Finally, human and mouse squamous cell carcinomas (SCCs) express NANOG and its levels positively correlate with those of AURKA in human head and neck SCCs. Together, these results implicate a lineage-restricted mitogenic role of NANOG in normal stratified epithelia and its derived carcinomas. Overall design: 2 conditions (genotypes) in 2 independent organs (esophagus and liver), 3 biological replicates per genotype. The experiment compares gene expression in Nanog overexpressing esophagus (Col1a1tetO-Nanog/+;Rosa26rtTA/+, indicated as TG) vs control esophagus (Col1a1+/+;Rosa26rtTA/+, indicated as CTR) and in Nanog overexpressing liver (Col1a1tetO-Nanog/+;Rosa26rtTA/+, indicated as TG) vs control liver (Col1a1+/+;Rosa26rtTA/+, indicated as CTR) all treated with 0.2 mg/ml doxycycline for 48 h. All mice of around 8 months of age.