對(duì)藥物治療或病毒感染的易感性從一個(gè)細(xì)胞到另一個(gè)細(xì)胞會(huì)有所不同,,即便是在放在一起培養(yǎng)的一組基因完全相同的細(xì)胞中也是如此,。這種異質(zhì)性在很大程度上一直被歸因于內(nèi)在噪音,如基因表達(dá)的變化或信號(hào)分子水平的波動(dòng),。
Snijder等人對(duì)大量共培養(yǎng)細(xì)胞進(jìn)行了定量分析,,并在細(xì)胞基本特點(diǎn)(如膜脂組成、或被一些而非另一些病毒感染的可感染性)與一個(gè)細(xì)胞的種群環(huán)境(例如,,它們是處在一個(gè)粘附細(xì)胞島的中心還是周邊)之間發(fā)現(xiàn)了決定性的聯(lián)系,。這項(xiàng)工作中采用的評(píng)估細(xì)胞群的計(jì)算機(jī)輔助方法也許還可用于藥物篩選。(生物谷Bioon.com)
生物谷推薦原始出處:
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.