A Caenorhabditis elegans model for epithelial-neuronal transdifferentiation
A Caenorhabditis elegans model for epithelial-neuronal transdifferentiation
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DOI：
10.1073/pnas.0712159105
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发表时间：
2008-03-11
影响因子：
11.1
通讯作者：
Greenwald, Iva
中科院分区：
文献类型：
--
作者：
Jarriault, Sophie;Schwab, Yannick;Greenwald, Iva
从基础科学和临床的角度来看，理解转分化（一种分化的细胞类型转化为另一种）都很重要。在秀丽隐杆线虫中，一个名为Y的上皮细胞最初是直肠的一部分，但后来似乎退出，迁移，然后成为一个名为PDA的运动神经元。在这里，我们表明，这代表了一个真正的转分化事件：Y有上皮标志，没有可检测的神经特征，和PDA没有残留的上皮特征。利用现有的突变体和激光显微手术，我们发现转分化不依赖于与邻近细胞的融合或需要Y细胞从直肠中迁移，其他直肠上皮细胞不能转分化，转分化需要EGL-5和SEM-4转录因子和LIN-12/Notch信号。我们的研究结果建立了Y-PDA转分化作为一个遗传学上易于处理的模型，用于破译体内细胞可塑性的机制。
Understanding transdifferentiation-the conversion of one differentiated cell type into another-is important from both basic science and clinical perspectives. In Caenorhabditis elegans, an epithelial cell named Y is initially part of the rectum but later appears to withdraw, migrate, and then become a motor neuron named PDA. Here, we show that this represents a bona fide transdifferentiation event: Y has epithelial hallmarks without detectable neural characteristics, and PDA has no residual epithelial characteristics. Using available mutants and laser microsurgery, we found that transdifferentiation does not depend on fusion with a neighboring cell or require migration of Y away from the rectum, that other rectal epithelial cells are not competent to transdifferentiate, and that transdifferentiation requires the EGL-5 and SEM-4 transcription factors and LIN-12/Notch signaling. Our results establish Y-to-PDA transdifferentiation as a genetically tractable model for deciphering the mechanisms underlying cellular plasticity in vivo.