西班牙心血管疾病国立研究中心Andrés Hidalgo团队绘制出炎症的行为性免疫图谱。相关论文于2022年1月5日在线发表在《自然》杂志上。
研究人员使用4D活体成像来记录了几十到几百个形态动力学参数，并描述了活跃炎症部位的单个白细胞动态。通过分析超过10万个细胞形状和轨迹的重建，研究人员获得了单个细胞的行为描述，并使用这些高维数据集来建立了行为图谱。这些图谱识别了发炎的皮肤和气管中的白细胞身份，并发现了血管内中性粒细胞的连续状态，包括被底层内皮围绕并与致病性炎症相关的状态。在24个小鼠突变体中进行的行为筛选确定了激酶Fgr是这种致病状态的驱动因素，对Fgr的干扰可保护小鼠免受炎症损伤。因此，行为图谱以高细胞分辨率报告了动态环境的不同属性。
据悉，单个细胞的转录和蛋白质组分析通过提供健康和疾病组织的细胞景观，彻底改变了对生物现象的解释。然而，这些方法并没有描述细胞不断改变其生化特性和下游"行为"输出的动态情况。
附：英文原文
Title: Behavioural immune landscapes of inflammation
Author: Crainiciuc, Georgiana, Palomino-Segura, Miguel, Molina-Moreno, Miguel, Sicilia, Jon, Aragones, David G., Li, Jackson Liang Yao, Madurga, Rodrigo, Adrover, Jos M., Aroca-Crevilln, Alejandra, Martin-Salamanca, Sandra, del Valle, Alfonso Serrano, Castillo, Sandra D., Welch, Heidi C. E., Soehnlein, Oliver, Graupera, Mariona, Snchez-Cabo, Ftima, Zarbock, Alexander, Smithgall, Thomas E., Di Pilato, Mauro, Mempel, Thorsten R., Tharaux, Pierre-Louis, Gonzlez, Santiago F., Ayuso-Sacido, Angel, Ng, Lai Guan, Calvo, Gabriel F., Gonzlez-Daz, Ivn, Daz-de-Mara, Fernando, Hidalgo, Andrs
Issue&Volume: 2022-01-05
Abstract: Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream ‘behavioural’ outputs3,4,5. 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.
DOI: 10.1038/s41586-021-04263-y
Source: https://www.nature.com/articles/s41586-021-04263-y
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
