Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia
Authors
Daniela Piazzolla, Adelaida R. Palla, Cristina Pantoja, Marta Can˜amero, Ignacio Perez de Castro, Sagrario Ortega, Gonzalo Go´mez-Lo´pez, Orlando Dominguez, Diego Megı´as, Giovanna Roncador8, Jose L. Luque-Garcia, Beatriz Fernandez-Tresguerres, Agustin F. Fernandez, Mario F. Fraga, Manuel Rodriguez-Justo, Miguel Manzanares, Marta Sa´nchez-Carbayo, Juana Marı´a Garcı´a-Pedrero, Juan P. Rodrigo, Marcos Malumbres & Manuel Serrano
Institution
CNIO
Country
Spain
Year
2014
Journal
Nature Communications
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.