Single-Cell Multimodal Profiling of Atherosclerosis Identifies CD200 as a Cell Surface Lineage Marker of Vascular Smooth Muscle Cells and Their Derived Cells

Abstract

therosclerotic cardiovascular disease is the leading cause of death worldwide. Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis because of their ability to transition phenotypically into either a protective or harmful state. However, the ability to identify and trace VSMCs and their progeny is limited because of a lack of well-defined VSMC surface markers. 1 Investigations into VSMCs must use lineagetracing mouse models, which are time-consuming, challenging to generate, and not feasible in humans. Here, we used cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) to characterize 119 cell surface proteins phenotypically in mouse atherosclerosis. We also performed CITE-seq in human atherosclerosis and found that CD200 is highly expressed and specific for VSMCs that persists even with phenotypic modulation.Mouse CITE-seq data are available in the National Center for Biotechnology Information Gene Expression Omnibus (database accession number GSE246779). All other data are available from the corresponding author upon request. The Institutional Animal Care and Use Committee of Columbia University approved all procedures (approval AABQ5576), and all procedures were in accordance with National Institutes of Health guidelines. The Institutional Review Board of Columbia University approved all human protocols under IRB AAAJ2765 and AAAR6796, with written informed consent obtained from all individuals.