Smurthwaite Cameron A, Williams Wesley, Fetsko Alexandra, Abbadessa Darin, Stolp Zachary D, Reed Connor W, Dharmawan Andre, Wolkowicz Roland
Department of Biology, San Diego State University.
Department of Biology, San Diego State University;
J Vis Exp. 2015 Apr 14(98):52452. doi: 10.3791/52452.
Fluorescent proteins, fluorescent dyes and fluorophores in general have revolutionized the field of molecular cell biology. In particular, the discovery of fluorescent proteins and their genes have enabled the engineering of protein fusions for localization, the analysis of transcriptional activation and translation of proteins of interest, or the general tracking of individual cells and cell populations. The use of fluorescent protein genes in combination with retroviral technology has further allowed the expression of these proteins in mammalian cells in a stable and reliable manner. Shown here is how one can utilize these genes to give cells within a population of cells their own biosignature. As the biosignature is achieved with retroviral technology, cells are barcoded 'indefinitely'. As such, they can be individually tracked within a mixture of barcoded cells and utilized in more complex biological applications. The tracking of distinct populations in a mixture of cells is ideal for multiplexed applications such as discovery of drugs against a multitude of targets or the activation profile of different promoters. The protocol describes how to elegantly develop and amplify barcoded mammalian cells with distinct genetic fluorescent markers, and how to use several markers at once or one marker at different intensities. Finally, the protocol describes how the cells can be further utilized in combination with cell-based assays to increase the power of analysis through multiplexing.
荧光蛋白、荧光染料及一般意义上的荧光团彻底改变了分子细胞生物学领域。特别是,荧光蛋白及其基因的发现使得能够构建用于定位的蛋白融合体、分析目的蛋白的转录激活及翻译,或者对单个细胞和细胞群体进行整体追踪。荧光蛋白基因与逆转录病毒技术相结合的应用,进一步实现了这些蛋白在哺乳动物细胞中稳定可靠的表达。此处展示了如何利用这些基因赋予细胞群体中的细胞各自的生物特征。由于生物特征是通过逆转录病毒技术实现的,细胞被“无限期地”编码。因此,它们可以在编码细胞的混合物中被单独追踪,并应用于更复杂的生物学应用中。在细胞混合物中追踪不同群体对于多重应用非常理想,例如针对多种靶点的药物发现或不同启动子的激活谱分析。该方案描述了如何巧妙地开发和扩增带有不同遗传荧光标记的编码哺乳动物细胞,以及如何同时使用几种标记或使用不同强度的一种标记。最后,该方案描述了如何将这些细胞与基于细胞的分析方法相结合,通过多重分析提高分析能力。