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Cross-tissue single cell landscape of human monocytes and macrophages in health and disease

ABSTRACT: Mononuclear phagocytes (MNP) encompass dendritic cells, monocytes and macrophages (MoMac), which exhibit antimicrobial, homeostatic and immunoregulatory functions. We integrated 178,651 MNP from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and defined conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialised cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumour-associated macrophage populations. Particularly, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumour periphery in a T cell-dependent manner via IFNg and CD40/CD40L-induced maturation from interferon-primed monocytes. IL4I1_Macs exhibited immune-suppressive characteristics through tryptophan degradation and promoted entry of regulatory T cell into tumours. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178209 | GEO | 2021/06/16

REPOSITORIES: GEO

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Project description:Macrophages play a critical role in the pathogenesis of many diseases, including rheumatoid arthritis, inflammatory bowel disease and atherosclerosis. Monocytes recruited into tissues from peripheral blood differentiate into macrophages. There is limited data concerning the global changes in the expression of genes during monocyte to macrophage, and how the patterns of change identify the mechanism contributing to differentiation or macrophage function. Employing the microarray technology, we examined the transcriptional profile of in vitro adherence-induced differentiation of primary human monocytes into macrophages. We found the significant up regulation of genes contributing to the functions of macrophage, including signature patterns defining the induction of genes contributing to immunity and defense; lipid, fatty acid and steroid metabolism; cell adhesion and; carbohydrate metabolism; amino acid metabolism and endocytosis. In contrast, a variety of transcription factors were down regulated during monocyte to macrophage differentiation, suggesting that transcriptional repression may be important for the transition from monocytes to macrophages. However, a limited number of transcription factors were up regulated, among these was C/EBPA, which may contribute to differentiation by regulating down stream genes, which a characteristic of differentiated macrophages. These observations suggest that examination of the transcriptional profile in monocytes and macrophages in patients may identify relevant therapeutic targets in diseases such as rheumatoid arthritis and atherosclerosis. Experiment Overall Design: Total 9 samples were analyzed. Repeats of 3 total RNA samples from monocytes at 0 hour, 3 samples from monocytes at 16 hours, and other 3 samples of monocytes at 168 hours after differentiation were collected. Following the Affymetrix protocol, 5-10 mg of high quality RNA was used to make labeled cRNA. The size distribution of fragmented and unfragmented labeled cRNA were assessed by 2100 Bioanalyzer (Agilent Technologies). 20mg of fragmented labeled cRNA was hybridized to Human U133A GeneChip at 45C for 18 hours. Affymetrix fluidics station was used to perform the washing and staining of the chips. GeneChip 3000 scanner system was used to scan the chips. The data were normalized by dCHIP method.

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Cross-tissue single cell landscape of human monocytes and macrophages in health and disease

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