永生神经细胞:概述

A. Calof
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Take, for example, the wealth of information that has been gained by studying molecular regulation of neuronal differentiation in the rat pheochromacytoma cell line, PC12: Studies of this cell line have been central to our understanding of the consequences——in terms of both cell division and terminal neuronal differentiation——of growth factor action on neural cells; they have led to the discovery and functional dissection of receptors for neurotrophic factors; and they have provided information that is central to our current understanding of the cytoplasmic signaling events that regulate neuronal differentiation. As much as has been gained from studying PC12s, however, these cells cannot be used in experiments attempting to identify the molecular events that underlie the differentiation of retinal neurons, or the de- velopment of oliogdendrocytes, or the regulation of odorant receptor expression. 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引用次数: 0

摘要

《神经协议:神经科学方法指南》第3期,175(1993):1058-6741/93美元编辑:永生化神经细胞:概述我们在识别调节脊椎动物神经系统发育和功能的分子方面取得快速进展的能力将大大有助于获得适当的神经细胞系。我所说的“合适”是指在神经系统中表现出许多不同种类细胞的分化特征和/或发育潜力的细胞系。例如,通过研究大鼠嗜铬细胞瘤细胞系PC12中神经元分化的分子调控获得了丰富的信息:对该细胞系的研究对于我们理解生长因子作用于神经细胞的后果(就细胞分裂和末梢神经元分化而言)至关重要;它们导致了神经营养因子受体的发现和功能解剖;他们提供的信息对我们目前对调节神经元分化的细胞质信号事件的理解至关重要。尽管从研究PC12s中获得了很多,但这些细胞不能用于试图确定视网膜神经元分化、少突胶质细胞发育或气味受体表达调节的分子事件的实验中。为了研究这些过程,我们真正想要的是能够代表特定神经细胞类型、处于特定发育阶段的细胞系。我相信,我们有理由谨慎乐观地认为,这种细胞系是可以制造出来的。本期《神经协议》的目的是向有兴趣尝试使神经细胞永生的读者介绍可用于制造神经细胞系的各种方法(以及这些方法的缺点和优点)。特别是对于那些对小鼠(大鼠和小鼠)神经细胞的免疫化感兴趣的人来说,现在有许多不同的方法可以采用。其中三种——生产携带靶向或诱导癌基因的转基因动物,用含癌基因的逆转录病毒感染分裂的前体细胞,以及原代神经元与神经母细胞-肿瘤细胞系的融合——构成了本期文章的重点。这三种方法都已经成功地产生了永生化的神经细胞系,其中一些具有高度分化的神经元特性。此外,研究人员还开发了从两种神经生物学家特别感兴趣的系统中制造神经细胞系的方法:非洲爪蟾(Xenopus laevis)和鸟类胚胎。两个小组在本期的文章中分享了他们在这一领域的专业知识。方法可能被证明是重要的评估永生化神经细胞的发展潜力也涵盖;一篇文章专门讨论了将细胞移植到啮齿动物的中枢神经系统。我们希望这期《神经协议》的出版将有助于其他研究人员开发和评估他们所需的细胞系。我感谢本期所有撰稿人的参与,感谢他们的热情和慷慨,提供了他们在神经生物学研究这一尚处于萌芽阶段的领域的工作的详细讨论。版权所有©1993学术出版社,Inc。保留任何形式的复制权利。175
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Immortalizing Neural Cells: An Overview
NEUROPROTOCOLS: A Companion to Methods in Neurosclences 3, 175 (1993) 1058-6741/93 $5.00 EDITORIAL Immortalizing Neural Cells: An Overview Our ability to make rapid progress in identifying the molecules that regulate vertebrate nervous system development and function would be greatly aided by the availability of appropriate neural cell lines. By “appropriate,’ I mean cell lines that exhibit the differentiated characteristics and/or developmental potential of the many different classes of cells in the nervous system. Take, for example, the wealth of information that has been gained by studying molecular regulation of neuronal differentiation in the rat pheochromacytoma cell line, PC12: Studies of this cell line have been central to our understanding of the consequences——in terms of both cell division and terminal neuronal differentiation——of growth factor action on neural cells; they have led to the discovery and functional dissection of receptors for neurotrophic factors; and they have provided information that is central to our current understanding of the cytoplasmic signaling events that regulate neuronal differentiation. As much as has been gained from studying PC12s, however, these cells cannot be used in experiments attempting to identify the molecular events that underlie the differentiation of retinal neurons, or the de- velopment of oliogdendrocytes, or the regulation of odorant receptor expression. For studying these processes, what we would really like would be cell lines rep- resentative of particular neural cell types, at specific stages in development. There is, I believe, reason to be cautiously optimistic that such cell lines can be made. It is the aim of this issue of NeuroProtocols to introduce to the reader interested in trying to immortalize neural cells something of the range of ap- proaches (and the disadvantages as well as the advantages of these approaches) available for making neural cell lines. Particularly for those interested in immor- talizing murine (rat and mouse) neural cells, there are now a number of different approaches that can be taken. Three of these-—production of transgenic animals carrying targeted or inducible oncogenes, infection of dividing precursor cells with oncogene—containing retroviruses, and fusion of primary neurons with neuroblas- toma cell lines——form the focus of articles in this issue. All three of these approaches have been successful in producing immortalized neural cell lines, some of which possess highly differentiated neuronal properties. Furthermore, investigators have also been developing approaches for making neural cell lines from two systems of particular interest to developmental neurobiologists: Xenopus laevis and the avian embryo. Two groups share their expertise in this area in articles in this issue. Approaches that may prove to be important in assessing the developmental po- tential of immortalized neural cells are also covered; one article deals specifically with grafting cells into the rodent central nervous system. It is our hope that publication of this issue of NeuroProtocols will be useful in helping other re- searchers to develop and evaluate the cell lines they require. I am grateful to all the contributors to this issue for taking part in this effort and for their enthusiasm and generosity in providing detailed discussions of their work in this still—embryonic area of neurobiological research. Anne L. Calof Guest Editor Copyright © 1993 by Academic Press, Inc. All rights of reproduction in any form reserved. 175
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