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.
