Csf1r-mApple Transgene Expression and Ligand Binding In Vivo Reveal Dynamics of CSF1R Expression within the Mononuclear Phagocyte System.
Csf1r-mApple Transgene Expression and Ligand Binding In Vivo Reveal Dynamics of CSF1R Expression within the Mononuclear Phagocyte System.
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DOI：
10.4049/jimmunol.1701488
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发表时间：
2018-03-15
期刊：
影响因子：
--
通讯作者：
Jenkins SJ
中科院分区：
文献类型：
--
作者：
Hawley CA;Rojo R;Raper A;Sauter KA;Lisowski ZM;Grabert K;Bain CC;Davis GM;Louwe PA;Ostrowski MC;Hume DA;Pridans C;Jenkins SJ
CSF 1是控制巨噬细胞数量的主要生长因子，但CSF 1受体的表达是否在单核吞噬细胞的离散群体之间存在差异仍不清楚。我们已经产生了Csf 1 r-mApple转基因荧光报告小鼠，结合谱系追踪，Alexa Fluor 647标记的CSF 1-Fc和CSF 1，以及缺乏远端启动子的150 bp片段的修饰的Δ Csf 1增强的青色荧光蛋白（ECFP）转基因，我们已经用于原位剖析单核吞噬细胞群体的分化和CSF 1反应性。与以前的Csf 1 r驱动的报告细胞系一致，Csf 1 r-mApple在血液单核细胞中表达，在组织巨噬细胞中表达水平更高，并且在整体安装或多光子显微镜下很容易检测到。在肝脏和腹腔中，标记的CSF 1的摄取在很大程度上反映了转基因表达，成熟巨噬细胞中的受体活性高于单核细胞，并且在常规树突状细胞中具有组织特异性表达。然而，CSF 1的摄取也不同的单核细胞和离散群体的组织巨噬细胞，这在巨噬细胞与它们的生存依赖CSF 1受体信号的水平，而不是转基因表达的程度。双Δ Csf 1 r-ECFP-Csf 1 r-mApple转基因小鼠区分了脑中的小胶质细胞亚群，并允许与肺泡巨噬细胞、肺单核细胞和常规树突状细胞不同的间质巨噬细胞成像。Csf 1 r-mApple小鼠和荧光标记的CSF 1将是研究巨噬细胞和CSF 1生物学的宝贵资源，它们与现有的基于EGFP的报告细胞系相容。
CSF1 is the primary growth factor controlling macrophage numbers, but whether expression of the CSF1 receptor differs between discrete populations of mononuclear phagocytes remains unclear. We have generated a Csf1r-mApple transgenic fluorescent reporter mouse that, in combination with lineage tracing, Alexa Fluor 647–labeled CSF1-Fc and CSF1, and a modified ΔCsf1–enhanced cyan fluorescent protein (ECFP) transgene that lacks a 150 bp segment of the distal promoter, we have used to dissect the differentiation and CSF1 responsiveness of mononuclear phagocyte populations in situ. Consistent with previous Csf1r-driven reporter lines, Csf1r-mApple was expressed in blood monocytes and at higher levels in tissue macrophages, and was readily detectable in whole mounts or with multiphoton microscopy. In the liver and peritoneal cavity, uptake of labeled CSF1 largely reflected transgene expression, with greater receptor activity in mature macrophages than monocytes and tissue-specific expression in conventional dendritic cells. However, CSF1 uptake also differed between subsets of monocytes and discrete populations of tissue macrophages, which in macrophages correlated with their level of dependence on CSF1 receptor signaling for survival rather than degree of transgene expression. A double ΔCsf1r-ECFP-Csf1r-mApple transgenic mouse distinguished subpopulations of microglia in the brain, and permitted imaging of interstitial macrophages distinct from alveolar macrophages, and pulmonary monocytes and conventional dendritic cells. The Csf1r-mApple mice and fluorescently labeled CSF1 will be valuable resources for the study of macrophage and CSF1 biology, which are compatible with existing EGFP-based reporter lines.
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影响因子：
30.5
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
通讯作者：
Prinz M
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
DOI：
10.1084/jem.20141539
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dal-Secco D;Wang J;Zeng Z;Kolaczkowska E;Wong CH;Petri B;Ransohoff RM;Charo IF;Jenne CN;Kubes P
通讯作者：
Kubes P
影响因子：
30.5
作者：
通讯作者：
--
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