Dissection of Influenza Infection In Vivo by Single-Cell RNA Sequencing.
Dissection of Influenza Infection In Vivo by Single-Cell RNA Sequencing.
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DOI：
10.1016/j.cels.2018.05.008
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发表时间：
2018-06-27
期刊：
影响因子：
9.3
通讯作者：
Gat-Viks I
中科院分区：
文献类型：
--
作者：
Steuerman Y;Cohen M;Peshes-Yaloz N;Valadarsky L;Cohn O;David E;Frishberg A;Mayo L;Bacharach E;Amit I;Gat-Viks I
流感病毒是世界范围内发病和死亡的主要原因。然而，细胞内病毒复制的影响和宿主反应在不同细胞类型中的变化仍然没有表征。在这里，我们使用单细胞RNA测序来研究肺组织细胞对体内流感感染的反应的异质性。在同一个单细胞中的病毒和宿主转录组的分析使我们能够解决与感染细胞相比，旁观者（暴露但未感染）的细胞异质性。我们发现，所有主要的免疫和非免疫细胞类型表现出感染细胞的实质性部分，尽管相对于上皮细胞病毒转录组负荷较低。我们表明，所有类型的细胞主要响应一个强大的通用转录反应，我们展示了新的标志物特异性流感感染，而不是旁观者细胞。这些发现为专门针对感染细胞的靶向治疗开辟了新途径。在体内流感感染期间宿主-病毒scRNA-seq的联合测量在多种免疫和非免疫细胞类型中感染的高流行率在感染细胞和旁观者细胞内存在广泛的细胞异质性感染细胞和旁观者细胞之间的通用和细胞类型特异性差异在同一单个细胞中宿主和病毒转录组的同时作图为研究宿主-病毒相互作用提供了框架。对来自体内流感感染的肺的细胞的分析揭示了通用和细胞类型特异性感染应答。通过分析旁观者（暴露但未感染）和感染细胞的细胞异质性，我们表征了流感感染特异性的新标志物，而不是旁观者。这些发现为专门针对感染细胞的靶向治疗开辟了新途径。
The influenza virus is a major cause of morbidity and mortality worldwide. Yet, both the impact of intracellular viral replication and the variation in host response across different cell types remain uncharacterized. Here we used single-cell RNA sequencing to investigate the heterogeneity in the response of lung tissue cells to in vivo influenza infection. Analysis of viral and host transcriptomes in the same single cell enabled us to resolve the cellular heterogeneity of bystander (exposed but uninfected) as compared with infected cells. We reveal that all major immune and non-immune cell types manifest substantial fractions of infected cells, albeit at low viral transcriptome loads relative to epithelial cells. We show that all cell types respond primarily with a robust generic transcriptional response, and we demonstrate novel markers specific for influenza-infected as opposed to bystander cells. These findings open new avenues for targeted therapy aimed exclusively at infected cells. Combined measurements of host-viral scRNA-seq during in vivo influenza infection High prevalence of infection in a variety of immune and non-immune cell types Extensive cellular heterogeneity exists within infected and bystander cells Generic and cell-type-specific differences between infected and bystander cells Simultaneous mapping of host and viral transcriptomes at the same single cell provides a framework to study host-viral interactions. Analysis of cells derived from lungs of in vivo influenza infection reveals both generic and cell-type-specific infection response. By analyzing the cellular heterogeneity of both bystander (exposed but uninfected) and infected cells, we characterize novel markers specific for influenza-infected as opposed to bystanders. These findings open new avenues for targeted therapy aimed exclusively at infected cells.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
44.1
作者：
Goswami, Ramansu;Majumdar, Tanmay;Barik, Sailen
通讯作者：
Barik, Sailen
影响因子：
5.9
作者：
Cristinelli, Sara;Ciuffi, Angela
通讯作者：
Ciuffi, Angela
影响因子：
7.7
作者：
Russell, Alistair B.;Trapnell, Cole;Bloom, Jesse D.
通讯作者：
Bloom, Jesse D.