A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte System
A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte System
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一种报告集落刺激因子1受体（CSF1R）蛋白表达的转基因品系为小鼠单核吞噬细胞系统提供了一个明确的标志物
DOI：
10.4049/jimmunol.2000835
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发表时间：
2020-12-01
影响因子：
4.4
通讯作者：
Hume, David A.
中科院分区：
文献类型：
--
作者：
Grabert, Kathleen;Sehgal, Anuj;Hume, David A.
单核吞噬细胞系统（MPS;祖细胞、单核细胞、巨噬细胞和经典树突细胞）的细胞增殖、分化和存活受来自M-CSF受体（CSF 1 R）的信号控制。已经使用许多表面标记物和转基因报告物鉴定了MPS谱系的细胞，但没有一个是通用的和谱系限制的。在这篇文章中，我们报告的开发和表征的CSF 1 R报告小鼠。将FusionRed（FRed）盒与CSF 1 R的C末端框内插入，通过T2 A可切割接头分开。插入没有影响CSF 1 R的表达或功能。CSF 1 R-FRed在单核细胞和巨噬细胞中表达，而在粒细胞和淋巴细胞中不表达。在骨髓中，CSF 1 R-FRed在谱系阴性造血干细胞中不存在，这与CSF 1 R在髓系定型中的直接作用有关。它在骨髓单核细胞和普通髓系祖细胞中高度表达，但在粒细胞-巨噬细胞祖细胞中显着降低。在骨髓切片中，在破骨细胞、CD 169（+）驻留巨噬细胞中也检测到CSF 1 R-FRed，与先前的mRNA分析一致，在巨核细胞中也检测到CSF 1 R-FRed。在淋巴组织中，CSF 1 R-FRed突出显示了不同的MPS群体，包括经典的树突状细胞。用组合的CSF 1 R-FRed/Csf 1 r-EGFP对小鼠的非淋巴组织进行整体封片成像，证实了CSF 1 R表达仅限于MPS细胞。这两种标志物突出了组织MPS细胞的显著丰度和规则分布，包括肌腱和骨骼肌内的新型巨噬细胞群体以及每个主要器官的间皮/浆膜/包膜表面。CSF 1 R-FRed小鼠为MPS细胞提供了一种具有高度特异性的新型报告基因。
The proliferation, differentiation, and survival of cells of the mononuclear phagocyte system (MPS; progenitors, monocytes, macrophages, and classical dendritic cells) are controlled by signals from the M-CSF receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters, but none is both universal and lineage restricted. In this article, we report the development and characterization of a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with the C terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells, arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly expressed in marrow monocytes and common myeloid progenitors but significantly lower in granulocyte-macrophage progenitors. In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169(+) resident macrophages, and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted diverse MPS populations, including classical dendritic cells. Whole mount imaging of nonlymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells, including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.