Stem cell division is regulated by the microRNA pathway
Stem cell division is regulated by the microRNA pathway
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DOI：
10.1038/nature03816
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发表时间：
2005-06-16
期刊：
影响因子：
64.8
通讯作者：
Ruohola-Baker, H
中科院分区：
文献类型：
--
作者：
Hatfield, SD;Shcherbata, HR;Ruohola-Baker, H
干细胞的关键特征之一是它们在大多数细胞处于静止状态的环境中长时间分裂的能力。因此，干细胞生物学中的一个关键问题是干细胞如何逃避细胞分裂停止信号。在这里，我们报告了microRNA（miRNA）途径（1-4）对果蝇生殖干细胞（GSC）分裂的适当控制的必要性。分析GSC突变体的dicer-1（dcr-1），miRNA生物合成所必需的双链RNaseIII，显示生殖细胞包囊产生率显着降低。这些dcr-1突变GSC表现出正常的身份，但在细胞周期控制中有缺陷。基于细胞周期标志物和遗传相互作用，我们得出结论，dcr-1突变GSCs在G1到S转换中延迟，这依赖于细胞周期蛋白依赖性激酶抑制剂Dacapo，这表明干细胞绕过正常G1/S检查点需要miRNA。因此，miRNA通路可能是使干细胞对环境信号不敏感的机制的一部分，环境信号通常在G1/S转换时停止细胞周期。
One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway(1-4) for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition.