267 - Side Specific Predisposition to The Vascular Disease Revealed by Single-cell RNA-Sequencing of Aorta Cells (ID 641)
Abstract
Background and Aims
Atherosclerosis is an inflammatory disease with complex plaque diversity. We performed scRNAseq to characterize in-depth the phenotypic and transcriptional diversity of CD45- and CD45+ cells derived from athero-prone (arch/roots) and athero-resistant (thoracic) aorta in Apoe-/- mice.
Methods
Eleven-week-old Apoe-/- mice were fed for 16 weeks normal or high cholesterol diet for 11 weeks. The aortic arch and roots were separated from the thoracic part of the aorta and digested separately. The cells were sorted based on CD45 expression and loaded onto C1 Single-Cell mRNA Seq chip for Illumina sequencing.
Results
Unsupervised clustering identified 7 (CD45- cells) and 12 (CD45+ cells) clusters respecting the side-specific predisposition to atherosclerosis (Figure 1). Clusters 0, 1, 2 and 5 composed of arch/roots CD45- cells expressed macrophages/VSMCs foam cells genes associated with VSMCs hyperplasia (BMP3), pro-atherogenic (Pf4), lipid uptake (GATA4), chondrocytes-specific (Chad), pro-inflammatory macrophage (SAA3, Hsd11b1, Pex5l, Slc10a6), thrombosis (F3, Gpx3) genes. In contrast thoracic aorta CD45- clusters 4 and 6 showed athero-resistant gene signature - muscle contraction (Tpm2, Cnn1, Myh11, Myl9, Mykl, Fbxo32, Acta2), anti-inflammatory (PTX3), anti-apoptotic (RASGRP2) genes. Arch/roots CD45+ clusters 1, 2 and 7 expressed genes linked to autoimmunity (Hspa1b ), inflammation (Lilra5, Ednrb, Cd209f, Ccl7, Ccl24), while thoracic CD45+ clusters 4, 8, 9 and 10 exhibited anti-atherogenic genes (Gpnmb, Slpi, Setmar, Ramp2, Tie1, Klk1) and noncanonical Wnt-signalling controlling inflammation, immunity, VSMCs contractile gene.
Conclusions
scRNAseq of atherosclerosis-prone and atherosclerosis-resistant side of the aorta revealed disease-relevant transcriptional signatures of CD45- and CD45+ cells, with implications for disease susceptibility, diagnosis and prevention.
