Behavioural immune landscapes of inflammation.
Behavioural immune landscapes of inflammation.
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DOI：
10.1038/s41586-021-04263-y
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发表时间：
2022-01
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
--
作者：
单个细胞的转录和蛋白质组学分析通过提供健康和患病组织的细胞景观，彻底改变了对生物现象的解释。然而，这些方法没有描述细胞不断改变其生化特性和下游“行为”输出的动态场景。在这里，我们使用4D实时成像来记录数十到数百个形态动力学参数，这些参数描述了活动性炎症部位单个白细胞的动态。通过分析超过100，000个细胞形状和轨迹的重建，我们获得了单个细胞的行为描述符，并使用这些高维数据集来构建行为景观。这些景观识别了发炎皮肤和气管中的白细胞身份，并揭示了血管内中性粒细胞状态的连续性，包括被底层内皮包围并与致病性炎症相关的大的无柄状态。在24个小鼠突变体中进行的行为筛选确定了激酶Fgr作为这种致病状态的驱动因素，并且干扰Fgr保护小鼠免受炎性损伤。因此，在高细胞分辨率的动态环境的行为景观报告不同的属性。
Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues,. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream ‘behavioural’ outputs, –. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution.
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DOI：
10.1126/science.1256478
发表时间：
2014-12-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sreeramkumar V;Adrover JM;Ballesteros I;Cuartero MI;Rossaint J;Bilbao I;Nácher M;Pitaval C;Radovanovic I;Fukui Y;McEver RP;Filippi MD;Lizasoain I;Ruiz-Cabello J;Zarbock A;Moro MA;Hidalgo A
通讯作者：
Hidalgo A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
1.2
作者：
Palomino-Segura, Miguel;Virgilio, Tommaso;Gonzalez, Santiago F.
通讯作者：
Gonzalez, Santiago F.
影响因子：
32.4
作者：
Adrover, Jose M.;del Fresno, Carlos;Hidalgo, Andres
通讯作者：
Hidalgo, Andres
影响因子：
100.3
作者：
Amit, Ido;Regev, Aviv;Hacohen, Nir
通讯作者：
Hacohen, Nir