Ecdysone and Mediator Change Energy Metabolism to Terminate Proliferation in Drosophila Neural Stem Cells
Ecdysone and Mediator Change Energy Metabolism to Terminate Proliferation in Drosophila Neural Stem Cells
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DOI：
10.1016/j.cell.2014.06.024
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发表时间：
2014-08-14
期刊：
影响因子：
64.5
通讯作者：
Knoblich, Juergen A.
中科院分区：
文献类型：
--
作者：
Homem, Catarina C. F.;Steinmann, Victoria;Knoblich, Juergen A.
干细胞在早期发育过程中高度丰富，但在大多数成年器官中成为稀有群体。导致干细胞在特定时间退出增殖的分子机制尚不清楚。在这里，我们表明，类固醇激素蜕皮激素和介体诱导的能量代谢的变化启动了导致果蝇神经干细胞细胞周期退出的不可逆级联事件。我们发现，神经母细胞需要及时诱导氧化磷酸化和线粒体呼吸链，才能将细胞周期从细胞生长中分离出来。这会导致神经母细胞体积的逐渐缩小，最终导致终末分化。脑瘤突变的神经母细胞没有经历这种收缩过程，并继续增殖，直到成年。我们的发现表明，细胞大小的控制可以通过全身激素信号来改变，并揭示了干细胞新陈代谢和增殖之间的独特联系。
Stem cells are highly abundant during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone ecdysone and the Mediator initiate an irreversible cascade of events leading to cell-cycle exit in Drosophila neural stem cells. We show that the timely induction of oxidative phosphorylation and the mitochondrial respiratory chain are required in neuroblasts to uncouple the cell cycle from cell growth. This results in a progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Brain tumor mutant neuroblasts fail to undergo this shrinkage process and continue to proliferate until adulthood. Our findings show that cell size control can be modified by systemic hormonal signaling and reveal a unique connection between metabolism and proliferation in stem cells.