Heterogeneity of macrophages in atherosclerosis revealed by single‐cell RNA sequencing

Abstract

Technology at the single-cell level has advanced dramatically in characterizing molecular heterogeneity. These technologies have enabled cell subtype diversity to be seen in all tissues, including atherosclerotic plaques. Critical in atherosclerosis pathogenesis and progression are macrophages. Previous studies have only How to cite this article: Yu L, Zhang Y, Liu C, et al. Heterogeneity of macrophages in atherosclerosis revealed by single-cell RNA sequencing.

Identification of a distinct cluster of GDF15highmacrophages exhibiting anti-inflammatory activities

“…Moreover, our results support the recent discovery of a population of monocyte-derived, GDF15-expressing macrophages in muscles, which have crucial roles in mediating tissue regeneration following inflammatory injuries 25 . We have showed that the GDF15 high macrophage does not strictly belong to either the M1 or the M2 phenotype 4 , highlighting the high degree of heterogeneity of macrophages which is more complex than that traditionally thought, as revealed by recent scRNA-seq studies 2,24 .…”

Macrophage mediators and mechanisms in cardiovascular disease

“…Recent integrative analysis of aortic single‐cell transcriptomes from 12 datasets of healthy and atherosclerotic mouse models as well as scRNAseq analysis of human atherosclerotic plaques has identified nine different macrophage populations in the atherosclerotic mouse aorta and eight different human macrophage subsets 39–41 . Comparison of gene expression patterns between the major human and murine macrophage subtypes as well as cross‐species dataset integration suggested similar transcriptional states and functional overlap demonstrating proof‐of‐concept for current murine models of atherosclerosis 42,43 . Gene expression analysis of MacAIRs and TREM2 + macrophages showed overlap of transcriptomes and enrichment for pathways of lipid metabolism in both, indicating that MacAIRs contribute to the pool of foamy macrophages 42 .…”

“…[39][40][41] Comparison of gene expression patterns between the major human and murine macrophage subtypes as well as cross-species dataset integration suggested similar transcriptional states and functional overlap demonstrating proof-of-concept for current murine models of atherosclerosis. 42,43 Gene expression analysis of MacAIRs and TREM2 + macrophages showed overlap of transcriptomes and enrichment for pathways of lipid metabolism in both, indicating that MacAIRs contribute to the pool of foamy macrophages. 42 Yet, MacAIRs are enriched in MHC-II transcripts, whereas TREM2 + macrophages show higher expression of the proinflammatory cytokines Tnf and IL-1b.…”

“…Finally, cavity macrophages with expression of Itgax , Ccr2 , H2‐Ab , Retnla , and Cd226 have been uncovered, whose function in atherosclerosis is unclear. A detailed description of macrophage subtypes in atherosclerosis is highlighted here 43 …”

A new "single" era of biomedicine and implications in disease research

“…These independent or combined "single" technologies have helped us not only to create a high-resolution SC type map of human tissues [127] and three-dimensional nuclear architecture, gene expression, and epigenetic modifications, [128] but also to assess and analyze immune cell differentiation, [129,130] to uncover cellular and molecular mechanisms and to discover new therapeutic targets for human diseases, [49,[131][132][133] in particular COVID-19 and CVDs, as well as to trace cancer progression. [134] It can be said that this is indeed a new "single" era of biomedicine and its current implications and research in both CVDs and COVID-19 [135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150] as well as others will definitely open a new beautiful future.…”