PMID- 31513013
OWN - NLM
STAT- MEDLINE
DCOM- 20200214
LR  - 20220517
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 8
DP  - 2019 Sep 12
TI  - Neural stem cell temporal patterning and brain tumour growth rely on oxidative 
      phosphorylation.
LID - 10.7554/eLife.47887 [doi]
LID - e47887
AB  - 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.
CI  - (c) 2019, van den Ameele and Brand.
FAU - van den Ameele, Jelle
AU  - van den Ameele J
AUID- ORCID: 0000-0002-2744-0810
AD  - The Gurdon Institute, Cambridge, United Kingdom.
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, United Kingdom.
FAU - Brand, Andrea H
AU  - Brand AH
AUID- ORCID: 0000-0002-2089-6954
AD  - The Gurdon Institute, Cambridge, United Kingdom.
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, United Kingdom.
LA  - eng
GR  - 092096/WT_/Wellcome Trust/United Kingdom
GR  - 092096/WT_/Wellcome Trust/United Kingdom
GR  - 105839/WT_/Wellcome Trust/United Kingdom
GR  - 103792/WT_/Wellcome Trust/United Kingdom
GR  - ALTF 1600_2014/European Molecular Biology Organization/International
GR  - 103792/WT_/Wellcome Trust/United Kingdom
GR  - 105839/WT_/Wellcome Trust/United Kingdom
GR  - C6946/A14492/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190912
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*pathology
MH  - Cell Differentiation
MH  - *Cell Proliferation
MH  - Disease Models, Animal
MH  - Drosophila
MH  - Glycolysis
MH  - Neural Stem Cells/*pathology
MH  - *Oxidative Phosphorylation
PMC - PMC6763261
OTO - NOTNLM
OT  - D. melanogaster
OT  - Warburg effect
OT  - brain tumours
OT  - developmental biology
OT  - neural stem cells
OT  - oxidative phosphorylation
OT  - regenerative medicine
OT  - stem cells
OT  - temporal patterning
OT  - tumour heterogeneity
COIS- Jv, AB No competing interests declared
EDAT- 2019/09/13 06:00
MHDA- 2020/02/15 06:00
PMCR- 2019/09/12
CRDT- 2019/09/13 06:00
PHST- 2019/04/23 00:00 [received]
PHST- 2019/09/11 00:00 [accepted]
PHST- 2019/09/13 06:00 [pubmed]
PHST- 2020/02/15 06:00 [medline]
PHST- 2019/09/13 06:00 [entrez]
PHST- 2019/09/12 00:00 [pmc-release]
AID - 47887 [pii]
AID - 10.7554/eLife.47887 [doi]
PST - epublish
SO  - Elife. 2019 Sep 12;8:e47887. doi: 10.7554/eLife.47887.