Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States
Year: 2024
Type: article
Study design: Observational Study
Abstract: Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. The Cell surface expression of CD14 and CD16 has historically identified them, however, recent single-cell studies have uncovered that they are much more heterogeneous than previously realized. We utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to describe the comprehensive transcriptional and phenotypic landscape of 437,126 monocytes. This high-dimensional multimodal approach identified vast phenotypic diversity and functionally distinct subsets, including IFN-responsive, MHCII hi , monocyte-platelet aggregates, and non-classical, as well as several subpopulations of classical monocytes. Using flow cytometry, we validated the existence of MHCII + CD275 + MHCII hi , CD42b + monocyte-platelet aggregates, CD16 + CD99 - non-classical monocytes, and CD99 + classical monocytes. Each subpopulation exhibited unique functions, developmental trajectories, transcriptional regulation, and tissue distribution. Moreover, we revealed alterations associated with cardiovascular disease (CVD) risk factors, including race, smoking, and hyperlipidemia, and the effect of hyperlipidemia was recapitulated in mouse models of elevated cholesterol. This integrative and cross-species comparative analysis provides a unique resource to compare alterations in monocytes in pathological conditions and offers insights into monocyte-driven mechanisms in CVD and the potential for targeted therapies. Summary Multimodal profiling provides a comprehensive phenotypic and transcriptional understanding of monocytes in health and cardiovascular disease risk states.
Source: Circulation Research
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G144283012, Computational and functional strategies to decipher lncRNAs in human atherosclerosis, Genomic Regulation and Translational Potential of a Novel Smooth Muscle Cell-Derived Cell Type in Atherosclerosis, Human VSMC mechanisms of action of ADAMTS7 locus for CAD, Elucidation of Tissue-Specific Transcriptomic Profiles in Cardio-metabolic Disease, BD Biosciences Influx, G6106290977, The role of Perk in atherosclerotic vascular smooth muscle cell modulation, Integrative analysis of bulk and single-cell RNA-seq data for cardiometabolic disease, Discovering Wdfy3 as a novel regulator of macrophage efferocytosis by genome-wide CRISPR screen, Statistical Methods for Single-Cell Transcriptomics, Clinical and Translational Science Award, Integrative genomic and functional genomic studies to connect variant to function for CAD GWAS loci, Smooth muscle cell-derived cell fates and cellular interactions in atherosclerotic plaque stability in disease progression and regression., Genomic Regulation and Translational Potential of a Novel Smooth Muscle Cell-Derived Cell Type in Atherosclerosis, Identification of smooth muscle cell genes causal in atherosclerotic plaque stability and cardiovascular disease risk, Postdoctoral Training in Arteriosclerosis Research, Cancer Center Support Grant
OpenAlex ID: W4401373424