The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis
Abstract
Rationale: It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they have been defined by the expression of a restricted number of markers. Objective: We have applied single-cell RNA sequencing as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. Method and Results: We performed single-cell RNA sequencing of total aortic CD45 + cells extracted from the nondiseased (chow fed) and atherosclerotic (11 weeks of high-fat diet) aorta of low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice. Unsupervised clustering singled out 13 distinct aortic cell clusters. Among the myeloid cell populations, resident-like macrophages with a gene expression profile similar to aortic resident macrophages were found in healthy and diseased aortas, whereas monocytes, monocyte-derived dendritic cells, and 2 populations of macrophages were almost exclusively detectable in atherosclerotic aortas, comprising inflammatory macrophages showing enrichment in Il1b and previously undescribed TREM2 hi (triggered receptor expressed on myeloid cells 2) macrophages showing enrichment in Trem2 . Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these 3 macrophage subsets and monocyte-derived dendritic cells and uncovered putative functions of each cell type. Notably, TREM2 hi macrophages seemed to be endowed with specialized functions in lipid metabolism and catabolism and presented a gene expression signature reminiscent of osteoclasts, suggesting a role in lesion calcification. TREM2 expression was moreover detected in human lesional macrophages. Importantly, these macrophage populations were present also in advanced atherosclerosis and in Apoe −/− aortas, indicating relevance of our findings in different stages of atherosclerosis and mouse models. Conclusions: These data unprecedentedly uncovered the transcriptional landscape and phenotypic heterogeneity of aortic macrophages and monocyte-derived dendritic cells in atherosclerotic and identified previously unrecognized macrophage populations and their gene expression signature, suggesting specialized functions. Our findings will open up novel opportunities to explore distinct myeloid cell populations and their functions in atherosclerosis.
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“In atherosclerosis, TREM2+ macrophages are enriched in atherosclerotic lesions and specialize in lipid catabolism (Cochain et al., 2018).”
From TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy (2020) · cites this paper as Cochain et al., 2018
In the citing paper
“LD accumulation in macrophages is associated with several inflammatory conditions (e.g., atherosclerosis) (4, 5), infectious diseases (e.g., mycobacterial infections) (6, 7), and cancer (8, 9).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [5]
In the citing paper
“LD accumulation in macrophages has also been documented in lipid-rich microenvironments in the peripheral, such as atherosclerosis plaques (5), white adipose tissue (10), and tumors (9).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [5]
In the citing paper
“Indeed, findings on unique macrophage subsets (such as TREM2+ macrophages) on the basis of single-cell analyses have uncovered unprecedented phenotypic heterogeneity of macrophages and monocyte-derived dendritic cells in atherosclerotic lesions and have defined a novel atlas of the immune cell repertoire in atherosclerosis135,154.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [154]
Citations
Cites
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Duewell, P., Kono, H., Rayner, K. J., Sirois, C. M., Vladimer, G., Bauernfeind, F. G., Abela, G. S., Franchi, L., Nuñez, G., Schnurr, M., et al. (2010) · Nature · doi:10.1038/nature08938 · Cited by 4,026
A gene atlas of the mouse and human protein-encoding transcriptomes
Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400782101 · Cited by 3,475
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979
Hashimoto, D., Chow, A., Noizat, C., Teo, P., Beasley, M. B., Leboeuf, M., Becker, C. D., See, P., Price, J., Lucas, D., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.004 · Cited by 2,311
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease
Ulland, T. K., Song, W. M., Huang, S. C.-C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.023 · Cited by 1,263
Macrophage Phenotype and Function in Different Stages of Atherosclerosis
Tabas, I., & Bornfeldt, K. E. (2016) · Circulation Research · doi:10.1161/circresaha.115.306256 · Cited by 1,121
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Immunity and Inflammation in Atherosclerosis
Wolf, D., & Ley, K. F. (2019) · Circulation Research · doi:10.1161/circresaha.118.313591 · Cited by 1,798
Self-citationCellMarker: a manually curated resource of cell markers in human and mouse
Zhang, X., Lan, Y., Xu, J., Quan, F., Zhao, E., Deng, C., Luo, T., Xu, L., Liao, G., Yan, M., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gky900 · Cited by 1,524
Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner
Jaitin, D. A., Adlung, L., Thaiss, C. A., Weiner, A., Li, B., Descamps, H., Lundgren, P., Bleriot, C., Liu, Z., Deczkowska, A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.054 · Cited by 1,377
Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
Bäck, M., Yurdagul, A., Tabas, I., Öörni, K., & Kovanen, P. T. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0169-2 · Cited by 1,341
Atherosclerosis: Recent developments
Björkegren, J., & Lusis, A. J. (2022) · Cell · doi:10.1016/j.cell.2022.04.004 · Cited by 1,344
Metadata
- Authors
- Cochain, C., Vafadarnejad, E., Arampatzi, P., Pelisek, J., Winkels, H., Ley, K., Wolf, D., Saliba, A.-E., & Zernecke, A.
- Affiliations
- Universitätsklinikum Würzburg (DE)
- Helmholtz Institute for RNA-based Infection Research (DE)
- Core Unit Systems Medicine (P.A.)
- TUM Klinikum (DE)
- La Jolla Institute for Immunology (US)
- From the Institute of Experimental Biomedicine (C.C., A.Z.)
- Corresponding author
- Cochain, Clément
- Vafadarnejad, Ehsan
- ORCID
- Venue
- Circulation Research
- Published
- 2018-06-08
- Volume
- 122
- Issue
- 12
- Pages
- 1661-1674
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2792855672
- Cited by
- 894
- References
- 54
- Citations by year
- 2026: 99 · 2025: 122 · 2024: 118 · 2023: 126 · 2022: 138 · 2021: 117 · 2020: 90 · 2019: 58 · 2018: 24
- FWCI
- 31.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL121697)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- atherosclerosis, macrophage heterogeneity, TREM2, monocyte-derived dendritic cells, inflammatory macrophages, tissue-resident macrophages, aortic calcification, lipid metabolism, Ldlr-deficient mice, ApoE-deficient mice, high-fat diet
- MeSH terms
- Animals, Aortic Diseases, Apolipoproteins E, B-Lymphocytes, Dendritic Cells, Humans, Leukocytes, Macrophages, Male, Monocytes, Phenotype, Receptors, LDL, T-Lymphocytes, Biomarkers, Sequence Analysis, RNA, Gene Expression Profiling, Atherosclerosis, Mice, Single-Cell Analysis
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