Single cell transcriptomics of Atlantic salmon (Salmo salar L.) liver reveals cellular heterogeneity and immunological responses to challenge by Aeromonas salmonicida.
Single cell transcriptomics of Atlantic salmon (Salmo salar L.) liver reveals cellular heterogeneity and immunological responses to challenge by Aeromonas salmonicida.
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DOI：
10.3389/fimmu.2022.984799
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发表时间：
2022
影响因子：
7.3
通讯作者：
Macqueen, Daniel J.
中科院分区：
文献类型：
--
作者：
Taylor, Richard S. S.;Daniels, Rose Ruiz;Dobie, Ross;Naseer, Shahmir;Clark, Thomas C. C.;Henderson, Neil C. C.;Boudinot, Pierre;Martin, Samuel A. M.;Macqueen, Daniel J.
肝脏是一个多任务的器官，对脊椎动物的健康具有重要的功能，包括代谢和免疫。与哺乳动物相反，我们对肝脏细胞异质性及其在调节免疫状态中的作用的理解在鱼类中仍然不清楚。为了解决这一知识缺口，我们生成了从大西洋鲑鱼（萨尔莫salar L.）肝脏分离的47，432个细胞核的转录组图谱。将对照鱼与用杀鲑气单胞菌（Aeromonassalmonicida）的致病菌株（全球水产养殖中的一种有问题的细菌病原体）攻击的那些鱼进行对比。我们确定了主要的肝细胞类型及其亚群，揭示了哺乳动物中使用的许多肝细胞标志物基因的保守性差，同时确定了肝细胞，淋巴和骨髓谱系中的新异质性。这包括多倍体肝细胞、包括γδ T细胞在内的多种T细胞群以及单核细胞/巨噬细胞和树突细胞的候选群。感染后，占优势的肝细胞群体从根本上重塑了其转录组，以激活急性期反应和其他防御功能，同时抑制代谢等常规功能。这些防御特化的肝细胞显示出控制蛋白质合成和分泌的基因的强烈激活，推测是为了支持急性期蛋白质释放到循环中。感染应答进一步涉及以免疫细胞特异性方式上调许多基因，反映病原体识别和杀伤、抗原呈递、吞噬作用、炎症调节、B细胞分化和T细胞活化中的功能。总的来说，这项研究极大地提高了我们对肝脏免疫和非免疫细胞在感染后宿主防御和代谢重塑中所发挥的多方面作用的理解，并提供了许多新的细胞特异性标记基因，为鱼类这一器官的未来研究提供了支持。
The liver is a multitasking organ with essential functions for vertebrate health spanning metabolism and immunity. In contrast to mammals, our understanding of liver cellular heterogeneity and its role in regulating immunological status remains poorly defined in fishes. Addressing this knowledge gap, we generated a transcriptomic atlas of 47,432 nuclei isolated from the liver of Atlantic salmon (Salmo salar L.) contrasting control fish with those challenged with a pathogenic strain of Aeromonas salmonicida, a problematic bacterial pathogen in global aquaculture. We identified the major liver cell types and their sub-populations, revealing poor conservation of many hepatic cell marker genes utilized in mammals, while identifying novel heterogeneity within the hepatocyte, lymphoid, and myeloid lineages. This included polyploid hepatocytes, multiple T cell populations including γδ T cells, and candidate populations of monocytes/macrophages and dendritic cells. A dominant hepatocyte population radically remodeled its transcriptome following infection to activate the acute phase response and other defense functions, while repressing routine functions such as metabolism. These defense-specialized hepatocytes showed strong activation of genes controlling protein synthesis and secretion, presumably to support the release of acute phase proteins into circulation. The infection response further involved up-regulation of numerous genes in an immune-cell specific manner, reflecting functions in pathogen recognition and killing, antigen presentation, phagocytosis, regulation of inflammation, B cell differentiation and T cell activation. Overall, this study greatly enhances our understanding of the multifaceted role played by liver immune and non-immune cells in host defense and metabolic remodeling following infection and provides many novel cell-specific marker genes to empower future studies of this organ in fishes.
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影响因子：
2.4
作者：
Cheng, Delfine;Morsch, Marco;Braet, Filip
通讯作者：
Braet, Filip
影响因子：
3.7
作者：
Bakken, Trygve E.;Hodge, Rebecca D.;Tasic, Bosiljka
通讯作者：
Tasic, Bosiljka
影响因子：
5.1
作者：
Andrews TS;Atif J;Liu JC;Perciani CT;Ma XZ;Thoeni C;Slyper M;Eraslan G;Segerstolpe A;Manuel J;Chung S;Winter E;Cirlan I;Khuu N;Fischer S;Rozenblatt-Rosen O;Regev A;McGilvray ID;Bader GD;MacParland SA
通讯作者：
MacParland SA
E 蛋白 TCF4 控制树突状细胞谱系规范的异构体特异性表达和反馈调节。
影响因子：
32.4
作者：
Grajkowska LT;Ceribelli M;Lau CM;Warren ME;Tiniakou I;Nakandakari Higa S;Bunin A;Haecker H;Mirny LA;Staudt LM;Reizis B
通讯作者：
Reizis B
DOI：
10.1016/0309-1651(80)90077-6
发表时间：
1980-01-01
期刊：
CELL BIOLOGY INTERNATIONAL REPORTS
影响因子：
--
作者：
BRASCH, K
通讯作者：
BRASCH, K