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A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
Published on: May 6, 2014
Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human
Alma Zernecke1, Florian Erhard2, Tobias Weinberger3,4
1Institute of Experimental Biomedicine, University Hospital Würzburg, Josef Schneider Str. 2, 97080 Würzburg, Germany.
Insights
This study refines mononuclear phagocyte nomenclature in atherosclerosis. Macrophages and dendritic cells (DCs) show conserved transcriptomic features in mouse and human disease, validating mouse models for atherosclerosis research.
Area of Science:
- Immunology
- Cardiovascular Research
- Single-cell Genomics
Background:
- Mononuclear phagocytes, including macrophages and dendritic cells (DCs), accumulate in atherosclerotic vessel walls.
- Accurate classification and understanding of these cells are crucial for atherosclerosis research.
Purpose of the Study:
- To refine the nomenclature of mononuclear phagocytes in atherosclerotic vessels.
- To compare the transcriptomic profiles of these cells in mouse and human atherosclerosis.
Main Methods:
- Integrated analysis of single-cell RNA sequencing (scRNA-seq) data from mouse and human atherosclerosis.
- Identification of distinct subpopulations based on transcriptomic signatures.
Main Results:
- Defined subpopulations of aortic resident, inflammatory, and foamy macrophages in mice.
- Identified Type 1 and Type 2 classical dendritic cells (cDC1, cDC2) and mature DCs in mice.
- Found conserved transcriptomic features in macrophages and DCs between mouse and human atherosclerosis, particularly the foamy macrophage signature.
Conclusions:
- Established a refined nomenclature for mononuclear phagocytes in atherosclerotic mouse vessels.
- Demonstrated conserved transcriptomic profiles of macrophages and DCs in mouse and human atherosclerosis.
- Highlighted the translational relevance of mouse models for studying mononuclear phagocytes in human atherosclerosis.
Aims:
Accumulation of mononuclear phagocytes [monocytes, macrophages, and dendritic cells (DCs)] in the vessel wall is a hallmark of atherosclerosis. Using integrated single-cell analysis of mouse and human atherosclerosis, we here aimed to refine the nomenclature of mononuclear phagocytes in atherosclerotic vessels and to compare their transcriptomic profiles in mouse and human disease.
Methods And Results:
We integrated 12 single-cell RNA-sequencing (scRNA-seq) datasets of immune cells isolated from healthy or atherosclerotic mouse aortas, and data from 11 patients (n = 4 coronary vessels, n = 7 carotid endarterectomy specimens) from two studies. Integration of mouse data identified subpopulations with discrete transcriptomic signatures within previously described populations of aortic resident (Lyve1), inflammatory (Il1b), as well as foamy (Trem2hi) macrophages. We identified unique transcriptomic features distinguishing aortic intimal resident macrophages from atherosclerosis-associated Trem2hi macrophages. Also, populations of Xcr1+ Type 1 classical DCs (cDC1), Cd209a+ cDC2, and mature DCs (Ccr7, Fscn1) with a 'mreg-DC' signature were detected. In humans, we uncovered macrophage and DC populations with gene expression patterns similar to those observed in mice. In particular, core transcripts of the foamy/Trem2hi signature (TREM2, SPP1, GPNMB, CD9) mapped to a specific population of macrophages in human lesions. Comparison of mouse and human data and direct cross-species data integration suggested transcriptionally similar macrophage and DC populations in mice and humans.
Conclusions:
We refined the nomenclature of mononuclear phagocytes in mouse atherosclerotic vessels, and show conserved transcriptomic features of macrophages and DCs in atherosclerosis in mice and humans, emphasizing the relevance of mouse models to study mononuclear phagocytes in atherosclerosis.
