Single-cell proteomic analysis of S-cerevisiae reveals the architecture of biological noise
Single-cell proteomic analysis of S-cerevisiae reveals the architecture of biological noise
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DOI：
10.1038/nature04785
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发表时间：
2006-06-15
期刊：
影响因子：
64.8
通讯作者：
Weissman, Jonathan S.
中科院分区：
文献类型：
--
作者：
Newman, John R. S.;Ghaemmaghami, Sina;Weissman, Jonathan S.
生物学的一个主要目标是提供细胞行为的定量描述。然而，由于测量蛋白质丰度及其变化的困难，这项任务受到了阻碍。在这里，我们提出了一种策略，将高通量流式细胞术和gfp标记酵母菌文库配对，以在单细胞分辨率下快速准确地监测蛋白质水平。在丰富和最小的培养基中，bbbb2500蛋白的散装蛋白丰度测量提供了细胞对这些条件反应的详细视图，并捕获了DNA微阵列分析未观察到的许多变化。我们的单细胞数据表明，蛋白质表达中的噪声是由信使rna的随机产生/破坏主导的。除了这一全球趋势之外，噪声中还存在着与蛋白质的转录模式及其功能密切相关的蛋白质特异性差异。例如，响应环境变化的蛋白质是嘈杂的，而参与蛋白质合成的蛋白质是安静的。因此，这些研究揭示了生物噪声的一个显著结构，并表明蛋白质噪声水平已经被选择来反映这种变化的成本和潜在收益。
A major goal of biology is to provide a quantitative description of cellular behaviour. This task, however, has been hampered by the difficulty in measuring protein abundances and their variation. Here we present a strategy that pairs high-throughput flow cytometry and a library of GFP-tagged yeast strains to monitor rapidly and precisely protein levels at single-cell resolution. Bulk protein abundance measurements of >2,500 proteins in rich and minimal media provide a detailed view of the cellular response to these conditions, and capture many changes not observed by DNA microarray analyses. Our single-cell data argue that noise in protein expression is dominated by the stochastic production/destruction of messenger RNAs. Beyond this global trend, there are dramatic protein-specific differences in noise that are strongly correlated with a protein's mode of transcription and its function. For example, proteins that respond to environmental changes are noisy whereas those involved in protein synthesis are quiet. Thus, these studies reveal a remarkable structure to biological noise and suggest that protein noise levels have been selected to reflect the costs and potential benefits of this variation.