Macrophages are involved in tissue homeostasis and are critical for innate immune responses, yet distinct macrophage populations in different tissues exhibit diverse gene expression patterns and biological processes. While tissue-specific macrophage epigenomic and transcriptomic profiles have been reported, proteomes of different macrophage populations remain poorly characterized. Here we use mass spectrometry and bulk RNA sequencing to assess the proteomic and transcriptomic patterns, respectively, of 10 primary macrophage populations from seven mouse tissues, bone marrow-derived macrophages and the cell line RAW264.7. The results show distinct proteomic landscape and protein copy numbers between tissue-resident and recruited macrophages. Construction of a hierarchical regulatory network finds cell-type-specific transcription factors of macrophages serving as hubs for denoting tissue and functional identity of individual macrophage subsets. Finally, Il18 is validated to be essential in distinguishing molecular signatures and cellular function features between tissue-resident and recruited macrophages in the lung and liver. In summary, these deposited datasets and our open proteome server (http://macrophage.mouseprotein.cn) integrating all information will provide a valuable resource for future functional and mechanistic studies of mouse macrophages.

巨噬细胞参与组织稳态，对先天免疫反应至关重要，但不同组织中不同的巨噬细胞群表现出不同的基因表达模式和生物过程。虽然已经报道了组织特异性巨噬细胞表观基因组学和转录组学概况，但不同巨噬细胞种群的蛋白质组特征仍然很差。在这里，我们使用质谱法和大量 RNA 测序来分别评估来自七个小鼠组织、骨髓来源的巨噬细胞和细胞系 RAW264.7 的 10 个原代巨噬细胞群的蛋白质组学和转录组学模式。结果显示组织驻留巨噬细胞和募集巨噬细胞之间存在明显的蛋白质组学景观和蛋白质拷贝数。分层调控网络的构建发现了巨噬细胞的细胞类型特异性转录因子，作为表示单个巨噬细胞亚群的组织和功能特性的中心。最后，Il18 被证实对于区分肺和肝脏中组织驻留和募集的巨噬细胞之间的分子特征和细胞功能特征至关重要。总之，这些存放的数据集和我们的开放蛋白质组服务器（http://macrophage.mouseprotein.cn）整合了所有信息，将为未来小鼠巨噬细胞的功能和机制研究提供宝贵的资源。Il18 被证实对于区分肺和肝脏中组织驻留和募集的巨噬细胞之间的分子特征和细胞功能特征至关重要。总之，这些存放的数据集和我们的开放蛋白质组服务器（http://macrophage.mouseprotein.cn）整合了所有信息，将为未来小鼠巨噬细胞的功能和机制研究提供宝贵的资源。Il18 被证实对于区分肺和肝脏中组织驻留和募集的巨噬细胞之间的分子特征和细胞功能特征至关重要。总之，这些存放的数据集和我们的开放蛋白质组服务器（http://macrophage.mouseprotein.cn）整合了所有信息，将为未来小鼠巨噬细胞的功能和机制研究提供宝贵的资源。