1. Cell Biology
  2. Stem Cells and Regenerative Medicine
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PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells

  1. María Inés Pérez Millán
  2. Michelle L Brinkmeier
  3. Amanda H Mortensen
  4. Sally A Camper  Is a corresponding author
  1. University of Michigan, United States
  2. University of Michigan-Ann Arbor, United States
Research Article
  • Cited 18
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Cite this article as: eLife 2016;5:e14470 doi: 10.7554/eLife.14470

Abstract

Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.

Article and author information

Author details

  1. María Inés Pérez Millán

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michelle L Brinkmeier

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Amanda H Mortensen

    Department of Human Genetics, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sally A Camper

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    For correspondence
    scamper@umich.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol of the University of Michigan. The protocol was approved by the University Committee on Use and Care of Animals (UCUCA) of the University of Michigan (PRO00004640).

Reviewing Editor

  1. Janet Rossant, University of Toronto, Canada

Publication history

  1. Received: January 16, 2016
  2. Accepted: June 24, 2016
  3. Accepted Manuscript published: June 28, 2016 (version 1)
  4. Version of Record published: July 11, 2016 (version 2)

Copyright

© 2016, Pérez Millán et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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