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.
Background Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis. Proteogenomic characterization and integrative proteomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. Methods We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 217 PDAC tumors with paired non-tumor adjacent tissues. In vivo functional experiments were performed to further illustrate the biological events related to PDAC tumorigenesis and progression. Results A comprehensive proteogenomic landscape revealed that TP53 mutations upregulated the CDK4-mediated cell proliferation process and led to poor prognosis in younger patients. Integrative multi-omics analysis illustrated the proteomic and phosphoproteomic alteration led by genomic alterations such as KRAS mutations and ADAM9 amplification of PDAC tumorigenesis. Proteogenomic analysis combined with in vivo experiments revealed that the higher amplification frequency of ADAM9 (8p11.22) could drive PDAC metastasis, though downregulating adhesion junction and upregulating WNT signaling pathway. Proteome-based stratification of PDAC revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Immune clustering defined a metabolic tumor subset that harbored FH amplicons led to better prognosis. Functional experiments revealed the role of FH in altering tumor glycolysis and in impacting PDAC tumor microenvironments. Experiments utilizing both in vivo and in vitro assay proved that loss of HOGA1 promoted the tumor growth via activating LARP7-CDK1 pathway. Conclusions This proteogenomic dataset provided a valuable resource for researchers and clinicians seeking for better understanding and treatment of PDAC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.