Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation
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DOI：
10.7554/elife.47887
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发表时间：
2019-09-12
期刊：
影响因子：
7.7
通讯作者：
Brand, Andrea H.
中科院分区：
文献类型：
--
作者：
van den Ameele, Jelle;Brand, Andrea H.
将癌症研究的进展转化为临床应用需要更好地了解正常细胞和肿瘤细胞在体内的代谢。许多努力都集中在理解糖酵解和氧化磷酸化（OxPhos）是如何支持增殖的，而它们对发育和肿瘤发生的其他方面的影响在很大程度上仍未被探索。我们发现，抑制神经干细胞（NSCs）或果蝇大脑肿瘤中的OxPhos不仅会减少增殖，还会影响干细胞行为的许多不同方面。在NSCs中，OxPhos功能障碍导致G(1)/ s期延长，导致时间模式延迟和神经元多样性降低。因此，NSCs不能进行终末分化，导致神经发生延长至成年期。同样，在脑肿瘤中，抑制OxPhos可减缓增殖并阻止分化，从而降低肿瘤异质性。因此，在体内，高增殖的干细胞和肿瘤细胞需要OxPhos来高效生长和产生多样性。
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.