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Meta-analysis of leukocyte diversity in atherosclerotic mouse aortas
- Source :
- Circulation Research, Circ Res
- Publication Year :
- 2020
- Publisher :
- Lippincott, Williams and Wilkins, 2020.
-
Abstract
- The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets—resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages—and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2 + foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, Pf4 , which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells.
- Subjects :
- Physiology
Aortic Diseases
030204 cardiovascular system & hematology
Biology
Article
03 medical and health sciences
0302 clinical medicine
Leukocytes
Animals
Mass cytometry
RNA-Seq
Aorta
030304 developmental biology
0303 health sciences
RNA
Atherosclerosis
Flow Cytometry
Molecular biology
Plaque, Atherosclerotic
Disease Models, Animal
Phenotype
Meta-analysis
Single-Cell Analysis
Cardiology and Cardiovascular Medicine
Transcriptome
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Circulation Research, Circ Res
- Accession number :
- edsair.doi.dedup.....867873c0e7afc25dc458fd2adc8778e0