Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation

  1. Jelle van den Ameele
  2. Andrea Brand  Is a corresponding author
  1. University of Cambridge, United Kingdom

Abstract

Translating advances in cancer research to clinical applications requires better insight into the metabolism of normal cells and tumour cells in vivo. Much effort has focused on understanding how glycolysis and oxidative phosphorylation (OxPhos) support proliferation, while their impact on other aspects of development and tumourigenesis remain largely unexplored. We found that inhibition of OxPhos in neural stem cells (NSCs) or tumours in the Drosophila brain not only decreases proliferation, but also affects many different aspects of stem cell behaviour. In NSCs, OxPhos dysfunction leads to a protracted G1/S-phase and results in delayed temporal patterning and reduced neuronal diversity. As a consequence, NSCs fail to undergo terminal differentiation, leading to prolonged neurogenesis into adulthood. Similarly, in brain tumours inhibition of OxPhos slows proliferation and prevents differentiation, resulting in reduced tumour heterogeneity. Thus, in vivo, highly proliferative stem cells and tumour cells require OxPhos for efficient growth and generation of diversity.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jelle van den Ameele

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2744-0810
  2. Andrea Brand

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    a.brand@gurdon.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2089-6954

Funding

Wellcome (103792)

  • Andrea Brand

Royal Society

  • Andrea Brand

European Molecular Biology Organization (ALTF 1600_2014)

  • Jelle van den Ameele

Wellcome (105839)

  • Jelle van den Ameele

Wellcome (092096)

  • Andrea Brand

Cancer Research UK (C6946/A14492)

  • Andrea Brand

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

Reviewing Editor

  1. Claude Desplan, New York University, United States

Version history

  1. Received: April 23, 2019
  2. Accepted: September 11, 2019
  3. Accepted Manuscript published: September 12, 2019 (version 1)
  4. Version of Record published: September 26, 2019 (version 2)

Copyright

© 2019, van den Ameele & Brand

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. Jelle van den Ameele
  2. Andrea Brand
(2019)
Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
eLife 8:e47887.
https://doi.org/10.7554/eLife.47887

Share this article

https://doi.org/10.7554/eLife.47887

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