对药物治疗或病毒感染的易感性从一个细胞到另一个细胞会有所不同,即便是在放在一起培养的一组基因完全相同的细胞中也是如此。这种异质性在很大程度上一直被归因于内在噪音,如基因表达的变化或信号分子水平的波动。
Snijder等人对大量共培养细胞进行了定量分析,并在细胞基本特点(如膜脂组成、或被一些而非另一些病毒感染的可感染性)与一个细胞的种群环境(例如,它们是处在一个粘附细胞岛的中心还是周边)之间发现了决定性的联系。这项工作中采用的评估细胞群的计算机辅助方法也许还可用于药物筛选。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 461, 520-523 (24 September 2009) | doi:10.1038/nature08282
Population context determines cell-to-cell variability in endocytosis and virus infection
Berend Snijder1,2, Raphael Sacher1,2, Pauli R?m?1, Eva-Maria Damm1, Prisca Liberali1 & Lucas Pelkmans1
1 Institute of Molecular Systems Biology, ETH Zurich (Swiss Federal Institute of Technology), Wolfgang Pauli-Strasse 16, CH-8093 Zurich, Switzerland
2 Zurich PhD Program in Molecular Life Sciences, Zurich, Switzerland
Correspondence to: Lucas Pelkmans1 Correspondence and requests for materials should be addressed to L.P.
Single-cell heterogeneity in cell populations arises from a combination of intrinsic and extrinsic factors1, 2, 3. This heterogeneity has been measured for gene transcription, phosphorylation, cell morphology and drug perturbations, and used to explain various aspects of cellular physiology4, 5, 6. In all cases, however, the causes of heterogeneity were not studied. Here we analyse, for the first time, the heterogeneous patterns of related cellular activities, namely virus infection, endocytosis and membrane lipid composition in adherent human cells. We reveal correlations with specific cellular states that are defined by the population context of a cell, and we derive probabilistic models that can explain and predict most cellular heterogeneity of these activities, solely on the basis of each cell's population context. We find that accounting for population-determined heterogeneity is essential for interpreting differences between the activity levels of cell populations. Finally, we reveal that synergy between two molecular components, focal adhesion kinase and the sphingolipid GM1, enhances the population-determined pattern of simian virus 40 (SV40) infection. Our findings provide an explanation for the origin of heterogeneity patterns of cellular activities in adherent cell populations.