Loss of foxo rescues stem cell aging in Drosophila germ line

Abstract

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.

Article and author information

Author details

  1. Filippo Artoni

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rebecca Kreipke

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ondina Palmeira

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Connor Dixon

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Zachary Goldberg

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Hannele Ruohola-Baker

    Department of Biochemistry, University of Washington, Seattle, United States
    For correspondence
    hannele@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5588-4531

Funding

National Institute of General Medical Sciences (R01-GM084947)

  • Filippo Artoni
  • Rebecca Kreipke
  • Ondina Palmeira
  • Connor Dixon
  • Zachary Goldberg

National Institute on Aging (Genetic Approaches to Aging Training Grant)

  • Rebecca Kreipke

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Fiona M Watt, King's College London, United Kingdom

Publication history

  1. Received: April 18, 2017
  2. Accepted: August 28, 2017
  3. Accepted Manuscript published: September 19, 2017 (version 1)
  4. Version of Record published: October 17, 2017 (version 2)

Copyright

© 2017, Artoni 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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  1. Filippo Artoni
  2. Rebecca Kreipke
  3. Ondina Palmeira
  4. Connor Dixon
  5. Zachary Goldberg
  6. Hannele Ruohola-Baker
(2017)
Loss of foxo rescues stem cell aging in Drosophila germ line
eLife 6:e27842.
https://doi.org/10.7554/eLife.27842
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