Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells.
Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells.
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DOI：
10.1083/jcb.201103018
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发表时间：
2011-05-16
期刊：
影响因子：
--
通讯作者：
Ip YT
中科院分区：
文献类型：
--
作者：
Amcheslavsky A;Ito N;Jiang J;Ip YT
缺乏 TSC 的果蝇肠道干细胞的过度细胞生长会阻碍进一步的细胞分裂。成年果蝇中肠中的肠干细胞（ISC）可以对损伤做出反应并支持修复。我们在本文中证明，结节性硬化症复合体 (TSC) 在平衡 ISC 生长和分裂中发挥着关键作用。先前的研究表明，TSC 突变的成虫盘细胞的生长和分裂速度加快。然而，我们在本文中报告说，成年果蝇中肠中 TSC 的损失导致形成更大的 ISC，从而停止细胞分裂。这些突变的 ISC 表达适当的干细胞标记，不分化，并且在细胞周期的多个步骤中存在缺陷。通过喂食雷帕霉素或减少 Myc 来减缓生长足以挽救分裂缺陷。 TSC突变体的肠道上皮结构比野生型组织更薄，并且突变体果蝇更容易受到组织损伤。因此，我们发现了成年 ISC 中 TSC 突变体的背景依赖性表型，即过度生长导致分裂抑制。
Excessive cell growth in Drosophila intestinal stem cells lacking TSC blocks further cell division. Intestinal stem cells (ISCs) in the adult Drosophila melanogaster midgut can respond to damage and support repair. We demonstrate in this paper that the tuberous sclerosis complex (TSC) plays a critical role in balancing ISC growth and division. Previous studies have shown that imaginal disc cells that are mutant for TSC have increased rates of growth and division. However, we report in this paper that loss of TSC in the adult Drosophila midgut results in the formation of much larger ISCs that have halted cell division. These mutant ISCs expressed proper stem cell markers, did not differentiate, and had defects in multiple steps of the cell cycle. Slowing the growth by feeding rapamycin or reducing Myc was sufficient to rescue the division defect. The TSC mutant guts had a thinner epithelial structure than wild-type tissues, and the mutant flies were more susceptible to tissue damage. Therefore, we have uncovered a context-dependent phenotype of TSC mutants in adult ISCs, such that the excessive growth leads to inhibition of division.
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