Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
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
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
- Claude Desplan, New York University, United States
Version history
- Received: April 23, 2019
- Accepted: September 11, 2019
- Accepted Manuscript published: September 12, 2019 (version 1)
- 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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