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Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry.
Winkels, Holger Ehinger, Erik Vassallo, Melanie Buscher, Konrad Dinh, Huy Q Kobiyama, Kouji Hamers, Anouk A J Cochain, Clément Vafadarnejad, Ehsan Saliba, Antoine-Emmanuel
Winkels, Holger
Ehinger, Erik
Vassallo, Melanie
Buscher, Konrad
Dinh, Huy Q
Kobiyama, Kouji
Hamers, Anouk A J
Cochain, Clément
Vafadarnejad, Ehsan
Saliba, Antoine-Emmanuel
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2018-03-15
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Abstract
Using single-cell RNA-sequencing of aortic leukocytes from chow diet- and Western diet-fed Apoe-/- and Ldlr-/- mice, we detected 11 principal leukocyte clusters with distinct phenotypic and spatial characteristics while the cellular repertoire in healthy aortas was less diverse. Gene set enrichment analysis on the single-cell level established that multiple pathways, such as for lipid metabolism, proliferation, and cytokine secretion, were confined to particular leukocyte clusters. Leukocyte populations were differentially regulated in atherosclerotic Apoe-/- and Ldlr-/- mice. We confirmed the phenotypic diversity of these clusters with a novel mass cytometry 35-marker panel with metal-labeled antibodies and conventional flow cytometry. Cell populations retrieved by these protein-based approaches were highly correlated to transcriptionally defined clusters. In an integrated screening strategy of single-cell RNA-sequencing, mass cytometry, and fluorescence-activated cell sorting, we detected 3 principal B-cell subsets with alterations in surface markers, functional pathways, and in vitro cytokine secretion. Leukocyte cluster gene signatures revealed leukocyte frequencies in 126 human plaques by a genetic deconvolution strategy. This approach revealed that human carotid plaques and microdissected mouse plaques were mostly populated by macrophages, T-cells, and monocytes. In addition, the frequency of genetically defined leukocyte populations in carotid plaques predicted cardiovascular events in patients.
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Circ Res. 2018 Jun 8;122(12):1675-1688. doi: 10.1161/CIRCRESAHA.117.312513. Epub 2018 Mar 15.
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MC5993603
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en
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1524-4571
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Attribution-NonCommercial-ShareAlike 4.0 International