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

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 asp...

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Detalles Bibliográficos
Autores principales: van den Ameele, Jelle, Brand, Andrea H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763261/
https://www.ncbi.nlm.nih.gov/pubmed/31513013
http://dx.doi.org/10.7554/eLife.47887
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author van den Ameele, Jelle
Brand, Andrea H
author_facet van den Ameele, Jelle
Brand, Andrea H
author_sort van den Ameele, Jelle
collection PubMed
description 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 G(1)/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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spelling pubmed-67632612019-10-02 Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation van den Ameele, Jelle Brand, Andrea H eLife Developmental Biology 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 G(1)/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. eLife Sciences Publications, Ltd 2019-09-12 /pmc/articles/PMC6763261/ /pubmed/31513013 http://dx.doi.org/10.7554/eLife.47887 Text en © 2019, van den Ameele and Brand http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
van den Ameele, Jelle
Brand, Andrea H
Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
title Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
title_full Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
title_fullStr Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
title_full_unstemmed Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
title_short Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
title_sort neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763261/
https://www.ncbi.nlm.nih.gov/pubmed/31513013
http://dx.doi.org/10.7554/eLife.47887
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