Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells
Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells
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通过 Ms4a3 表达历史追踪单核细胞衍生细胞的命运图谱
DOI：
10.1016/j.cell.2019.08.009
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发表时间：
2019-09-05
期刊：
影响因子：
64.5
通讯作者：
Ginhoux, Florent
中科院分区：
文献类型：
--
作者：
Liu, Zhaoyuan;Gu, Yaqi;Ginhoux, Florent
大多数组织驻留巨噬细胞(RTM)群体由胚胎造血波播种，并在成年后独立于骨髓贡献而自我维持。然而，RTM的一部分不断被单核细胞取代，与胚胎RTM相比，它们的功能尚不清楚。循环单核细胞在动态平衡、炎症和疾病期间对RTM替代的作用的动力学和程度一直备受争议。在这里，我们确定Ms4a3是一个由粒-单核细胞祖细胞(GMP)表达的特异性基因，并随后产生了Ms4a3(TDT)报告器、Ms4a3(CRE)和Ms4a3(CreERT2)命运映射模型。这些模型有效地追踪单核细胞和粒细胞，但没有淋巴细胞或组织树突状细胞。使用这些模型，我们精确地量化了单核细胞在动态平衡和炎症期间对RTM池的贡献。对单核细胞来源的细胞的明确鉴定将使未来在任何条件下研究它们的功能成为可能。
Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3(TdT) reporter, Ms4a3(Cre), and Ms4a3(CreERT2) fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous idenification of monocyte-derived cells will permit future studies of their function under any condition.