Abstract 14574: Cellular Population Evolution and Differential Gene Expression Patterns of Human Aorta in Different Life Stages Revealed by Single-Cell Transcriptome Analysis

Abstract

Introduction: Cellular characteristics and gene expression patterns of human aortic tissue is biological basis for understanding pathogenesis of aortic diseases, and still unclear. Our aim was to investigate cellular population evolution and differential gene expression patterns of human aorta in different life stages. Methods: Single-cell transcriptome sequencing was applied to study differential gene expression pattern and cellular population of entire ascending aortic walls from six healthy donors: 4 in younger group (3 months, 1 year, 3 and 12 years of age) and 2 in aged group (57 and 58 years of age), 50% males. Pseudotime trajectory and cell-to-cell communication analysis of the annotated cell subclusters were preformed to analyze development and evolution of cells. Histological examination of the specimens was carried out by using routine and immunohistochemical stains to validate findings of single-cell sequencing. Results: Ten main cell types (27 high-resolution subtypes, totally 65,470 cells) were identified in the specimens, including endothelial cell, smooth muscle cell, fibroblast, mesenchymal cell, mesenchymal-fibroblast cell, macrophage, and T cell. As donors age increased, proportion of non-immune cells such as endothelial cell decreased from 22.47% to 10.37%, smooth muscle cell from 20.40% to 18.50%, fibroblasts from 30.21% to 13.29%, and mesenchymal cell from 5.12% to 1.55%; while proportion of immune cells such as macrophages increased from 10.94 % to 17.02 % ; and T cells from 3.80% to 26.01%. Synthetic smooth muscle cell, fibroblasts of extracellular matrix synthesis, and mesenchymal cells expressing osteocalcin/matrix Gla family genes (MAG, logFC: 4.0, P<0.01) were significantly increased in the aged donors as well as the ligand-receptor pairs between macrophages and T cells mainly in endocrine resistance related pathway. M1 (CD86) and M2 (CD163) macrophage signature antibodies were slightly elevated in the aged donors which correlated well to the findings from single-cell sequencing. Conclusions: Cellular population and differential gene expression patterns in human aortic tissue are under dynamic evolution in the life circle. Immune cells infiltration increases while non-immune cells decrease as age increases.