Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria
Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria
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DOI：
10.1016/j.devcel.2005.02.014
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发表时间：
2005-05-01
影响因子：
11.8
通讯作者：
Alvarado, AS
中科院分区：
文献类型：
--
作者：
Reddien, PW;Bermange, AL;Alvarado, AS
一个多世纪以来，涡虫一直是再生、组织稳态和干细胞生物学研究的经典模型系统，但历史上它们一直无法进行广泛的基因操作。在这里，我们利用 RNA 介导的遗传干扰 (RNAi) 将大规模基因抑制研究引入经典涡虫系统。筛选了1065个基因。与 240 个基因的 RNAi 相关的表型识别了再生过程中的许多特定缺陷，并定义了涡虫在基因扰动后表现出的缺陷的主要类别。我们评估了用 RNAi 抑制基因对完整动物组织稳态和截肢动物干细胞（新生细胞）增殖的影响，确定了候选干细胞、再生和稳态调节因子。我们的研究证明了 RNAi 在系统探索所研究生物体基因功能方面的巨大潜力，并将涡虫建立为干细胞、再生和组织稳态分子遗传学研究的强大模型。
Planarians have been a classic model system for the study of regeneration, tissue homeostasis, and stem cell biology for over a century, but they have not historically been accessible to extensive genetic manipulation. Here we utilize RNA-mediated genetic interference (RNAi) to introduce large-scale gene inhibition studies to the classic planarian system. 1065 genes were screened. Phenotypes associated with the RNAi of 240 genes identify many specific defects in the process of regeneration and define the major categories of defects planarians display following gene perturbations. We assessed the effects of inhibiting genes with RNAi on tissue homeostasis in intact animals and stem cell (neoblast) proliferation in amputated animals identifying candidate stem cell, regeneration, and homeostasis regulators. Our study demonstrates the great potential of RNAi for the systematic exploration of gene function in understudied organisms and establishes planarians as a powerful model for the molecular genetic study of stem cells, regeneration, and tissue homeostasis.