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

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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.

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

Article and author information

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Jelle van den Ameele

The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2744-0810
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.

"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.

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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.