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

Author

Listed:
  • Daniela Piazzolla

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO))

  • Adelaida R. Palla

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO))

  • Cristina Pantoja

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO))

  • Marta Cañamero

    (Histopathology Core Unit, CNIO)

  • Ignacio Perez de Castro

    (CNIO)

  • Sagrario Ortega

    (Transgenic Mice Core Unit, CNIO)

  • Gonzalo Gómez-López

    (Bioinformatics Unit, CNIO)

  • Orlando Dominguez

    (Genomics Core Unit, CNIO)

  • Diego Megías

    (Confocal Microscopy Core Unit, CNIO)

  • Giovanna Roncador

    (Monoclonal Antibodies Core Unit, Spanish National Cancer Research Centre (CNIO))

  • Jose L. Luque-Garcia

    (Faculty of Chemistry, Complutense University of Madrid)

  • Beatriz Fernandez-Tresguerres

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Agustin F. Fernandez

    (Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo)

  • Mario F. Fraga

    (Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo
    Centro Nacional de Biotecnología/CNB-CSIC)

  • Manuel Rodriguez-Justo

    (University College Hospital)

  • Miguel Manzanares

    (Centro Nacional de Investigaciones Cardiovasculares (CNIC))

  • Marta Sánchez-Carbayo

    (CIC bioGUNE, Bizkaia Technology Park, Derio 48160 and Ikerbasque, Basque Foundation for Science)

  • Juana María García-Pedrero

    (Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo)

  • Juan P. Rodrigo

    (Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo)

  • Marcos Malumbres

    (CNIO)

  • Manuel Serrano

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO))

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.

Suggested Citation

  • Daniela Piazzolla & Adelaida R. Palla & Cristina Pantoja & Marta Cañamero & Ignacio Perez de Castro & Sagrario Ortega & Gonzalo Gómez-López & Orlando Dominguez & Diego Megías & Giovanna Roncador & Jos, 2014. "Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia," Nature Communications, Nature, vol. 5(1), pages 1-14, September.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5226
    DOI: 10.1038/ncomms5226
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    Cited by:

    1. Nika Rajabian & Izuagie Ikhapoh & Shahryar Shahini & Debanik Choudhury & Ramkumar Thiyagarajan & Aref Shahini & Joseph Kulczyk & Kendall Breed & Shilpashree Saha & Mohamed Alaa Mohamed & Susan B. Udin, 2023. "Methionine adenosyltransferase2A inhibition restores metabolism to improve regenerative capacity and strength of aged skeletal muscle," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Naveen Kumar & Pon Ganish Prakash & Christian Wentland & Shilpa Mary Kurian & Gaurav Jethva & Volker Brinkmann & Hans-Joachim Mollenkopf & Tobias Krammer & Christophe Toussaint & Antoine-Emmanuel Sali, 2024. "Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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