Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from ...13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.
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•Cross-tissue integration of scRNA from monocytes and macrophages in health and disease•Conserved gene signatures of mononuclear phagocyte populations in human tissues•IL4I1+PD-L1+IDO1+ and TREM2+ TAM subsets accumulate in human tumors•IL4I1+PD-L1+IDO1+ TAM in the tumor periphery exhibit immunosuppressive characteristics
Mulder et al. integrate 178,651 human mononuclear phagocytes (MNPs) from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE) that enables the definition of conserved gene signatures of MNP populations. This integrated approach provides a robust, online-available platform (https://gustaveroussy.github.io/FG-Lab/) for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.
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