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Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease
Open accessAbstract
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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“Considering that the functional diversity of macrophages during polarization have recently been reported36,61, our arguments need to be further validated by using single-cell phenotypic analysis, which will allow us to delineate the heterogeneity of infiltrating”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [61]
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Metadata
- Authors
- Mulder, K., Patel, A. A., Kong, W. T., Piot, C., Halitzki, E., Dunsmore, G., Khalilnezhad, S., Irac, S. E., Dubuisson, A., Chevrier, M., Zhang, X. M., Tam, J. K. C., Lim, T. K. H., Wong, R. M. M., Pai, R., Khalil, A. I. S., Chow, P. K. H., Wu, S. Z., Al-Eryani, G., Roden, D., Swarbrick, A., Chan, J. K. Y., Albani, S., Derosa, L., Zitvogel, L., Sharma, A., Chen, J., Silvin, A., Bertoletti, A., Blériot, C., Dutertre, C.-A., & Ginhoux, F.
- Affiliations
- Inserm (FR)
- Singapore Immunology Network (SG)
- Agency for Science, Technology and Research (SG)
- National University of Singapore (SG)
- Singapore General Hospital (SG)
- Nanyang Technological University (SG)
- National Cancer Centre Singapore (SG)
- Garvan Institute of Medical Research (AU)
- Institut Gustave Roussy (FR)
- Duke-NUS Medical School (SG)
- Corresponding author
- Dutertre, Charles-Antoine
- Ginhoux, Florent
- ORCID
- Mulder, Kevin
- Patel, Amit Ashok
- Kong, Wan Ting
- Piot, Cécile
- Halitzki, Evelyn
- Dunsmore, Garett
- Irac, Sergio Erdal
- Dubuisson, Agathe
- Zhang, Xiao Meng
- Tam, John Kit Chung
- Lim, Tony Kiat Hon
- Khalil, Ahmed Ibrahim Samir
- Chow, Pierce Kah Hoe
- Roden, Daniel
- Swarbrick, Alexander
- Chan, Jerry Kok Yen
- Albani, Salvatore
- Derosa, Lisa
- Zitvogel, Laurence
- Sharma, Ankur
- Chen, Jinmiao
- Silvin, Aymeric
- Bertoletti, Antonio
- Blériot, Camille
- Dutertre, Charles-Antoine
- Ginhoux, Florent
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 54
- Issue
- 8
- Pages
- 1883-1900.e5
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W3187504732
- Cited by
- 678
- References
- 85
- Citations by year
- 2026: 137 · 2025: 168 · 2024: 162 · 2023: 128 · 2022: 77 · 2021: 6
- FWCI
- 34.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- National University of Singapore (submittedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- monocytes, macrophages, mononuclear phagocytes, tumor-associated macrophages, PD-L1, IDO1, IL4I1, interferon-gamma, CD40/CD40L, regulatory T cells, tryptophan degradation, tumor immunosuppression, inflammation, dendritic cells
- MeSH terms
- Tumor-Associated Macrophages, COVID-19, Arthritis, Rheumatoid, Dendritic Cells, Humans, Interferon-gamma, Liver Cirrhosis, Macrophages, Monocytes, Neoplasms, Gene Expression, RNA, Small Cytoplasmic, Gene Expression Profiling, T-Lymphocytes, Regulatory, L-Amino Acid Oxidase, Single-Cell Analysis, Transcriptome
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