Conover J C, Ip N Y, Poueymirou W T, Bates B, Goldfarb M P, DeChiara T M, Yancopoulos G D
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Development. 1993 Nov;119(3):559-65. doi: 10.1242/dev.119.3.559.
Ciliary neurotrophic factor was discovered based on its ability to support the survival of ciliary neurons, and is now known to act on a variety of neuronal and glial populations. Two distant relatives of ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M, mimic ciliary neurotrophic factor with respect to its actions on cells of the nervous system. In contrast to ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M also display a broad array of actions on cells outside of the nervous system. The overlapping activities of leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor can be attributed to shared receptor components. The specificity of ciliary neurotrophic factor for cells of the nervous system results from the restricted expression of the alpha component of the ciliary neurotrophic factor receptor complex, which is required to convert a functional leukemia inhibitory factor/oncostatin M receptor complex into a ciliary neurotrophic factor receptor complex. The recent observation that the alpha component of the ciliary neurotrophic factor receptor complex is expressed by very early neuronal precursors suggested that ciliary neurotrophic factor may act on even earlier precursors, particularly on cells previously thought to be targets for leukemia inhibitory factor action. Here we show the first example of ciliary neurotrophic factor responsiveness in cells residing outside of the nervous system by demonstrating that embryonic stem cells express a functional ciliary neurotrophic factor receptor complex, and that ciliary neurotrophic factor is similar to leukemia inhibitory factor in its ability to maintain the pluripotentiality of these cells.
睫状神经营养因子是基于其支持睫状神经元存活的能力而被发现的，现在已知它作用于多种神经元和神经胶质细胞群体。睫状神经营养因子的两个远亲，白血病抑制因子和制瘤素M，在对神经系统细胞的作用方面模拟睫状神经营养因子。与睫状神经营养因子不同，白血病抑制因子和制瘤素M对神经系统以外的细胞也表现出广泛的作用。白血病抑制因子、制瘤素M和睫状神经营养因子的重叠活性可归因于共享的受体成分。睫状神经营养因子对神经系统细胞的特异性源于睫状神经营养因子受体复合物α成分的限制性表达，该成分是将功能性白血病抑制因子/制瘤素M受体复合物转化为睫状神经营养因子受体复合物所必需的。最近的观察发现，睫状神经营养因子受体复合物的α成分由非常早期的神经元前体细胞表达，这表明睫状神经营养因子可能作用于更早的前体细胞，特别是那些以前被认为是白血病抑制因子作用靶点的细胞。在这里，我们通过证明胚胎干细胞表达功能性睫状神经营养因子受体复合物，以及睫状神经营养因子在维持这些细胞的多能性方面与白血病抑制因子相似，展示了神经系统外细胞对睫状神经营养因子反应性的首个例子。
