Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.
Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.
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DOI：
10.1016/j.jhep.2016.05.037
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发表时间：
2016-10
影响因子：
25.7
通讯作者：
Kaye PM
中科院分区：
文献类型：
--
作者：
Beattie L;Sawtell A;Mann J;Frame TCM;Teal B;de Labastida Rivera F;Brown N;Walwyn-Brown K;Moore JWJ;MacDonald S;Lim EK;Dalton JE;Engwerda CR;MacDonald KP;Kaye PM
枯否细胞（KCs），肝脏的常驻组织巨噬细胞，在清除到达体循环的病原体和其他颗粒物质中起着至关重要的作用。最近的研究已经确定KC作为卵黄囊来源的驻留巨噬细胞群体，其在稳态下独立于单核细胞补充。虽然现在已经确定，在局部组织损伤后，骨髓来源的单核细胞可以浸润组织并分化成巨噬细胞，但新分化的巨噬细胞在功能上与它们所取代的KC相似的程度尚未得到广泛研究。我们研究了两个人口的KC使用活体显微镜，形态分析和基因表达谱。离子稳态基因签名，包括与清道夫受体功能和细胞外基质沉积相关的基因，允许这两种KC亚型之间的歧视。由于遗传毒性损伤，骨髓来源的“KCs”蓄积，类似于但不完全相同于其卵黄囊对应物。反映清道夫受体的差异表达，卵黄囊来源的KC更有效地积累乙酰化低密度脂蛋白，而令人惊讶的是，他们比骨髓来源的KC时，评估吸收的一系列细菌病原体。两种KC种群在以下方面几乎不可区分：i）对脂多糖攻击的反应，ii）对衰竭红细胞的吞噬作用，iii）它们抑制杜氏利什曼原虫（一种KC嗜性细胞内寄生虫）感染和直接肉芽肿形成的能力。骨髓来源的KC在大多数但不是所有方面局部分化为类似于卵黄囊来源的KC，这对感染性疾病、肝损伤和骨髓移植的模型具有意义。此外，我们描述的基因签名添加到可用于区分KC亚群的基础上，他们的本体论的工具。肝脏巨噬细胞在控制肝脏感染和与慢性肝病相关的病理学中起主要作用。最近表明，肝脏巨噬细胞可以有两种不同的来源，然而，这些群体在功能上不同的程度仍有待充分解决。我们的研究表明，虽然肝脏巨噬细胞有许多共同的特征，但无论它们的来源如何，在功能上存在一些细微的差异。基因表达数据可从欧洲生物信息学研究所ArrayExpress数据存储库（登录号E-MTAB-4954）获得。
Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types. Bone marrow derived “KCs” accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide challenge, ii) phagocytosis of effete red blood cells and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. Bone marrow-derived KCs differentiate locally to resemble yolk sac-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology. Liver macrophages play a major role in the control of infections in the liver and in the pathology associated with chronic liver diseases. It was recently shown that liver macrophages can have two different origins, however, the extent to which these populations are functionally distinct remains to be fully addressed. Our study demonstrates that whilst liver macrophages share many features in common, regardless of their origin, some subtle differences in function exist. Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954).
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影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan
影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK
影响因子：
64.5
作者：
Lavin Y;Winter D;Blecher-Gonen R;David E;Keren-Shaul H;Merad M;Jung S;Amit I
通讯作者：
Amit I
DOI：
10.1523/jneurosci.6344-09.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alexander JK;Sagher D;Krivoshein AV;Criado M;Jefford G;Green WN
通讯作者：
Green WN
影响因子：
5.4
作者：
Chen, Yunying;Wermeling, Fredrik;Karlsson, Mikael C. I.
通讯作者：
Karlsson, Mikael C. I.