Transcriptome dynamics during cholesterol-induced transdifferentiation of human coronary artery smooth muscle cells: A Gene Ontology-centric clustering approach

Abstract

Macrophage-like cells derived from vascular smooth muscle cells (SMCs) play critical roles in atherogenesis, and DNA hydroxymethylation was implicated in transdifferentiation. We examined transcriptomes and (hydroxy)methylomes of human coronary artery SMCs during cholesterol-induced transdifferentiation. A unique approach of exhaustive identification of differentially expressed genes followed by Gene Ontology-centric clustering facilitated deeper understanding of multifaceted modulations of genes involved in extracellular matrix organization, angiogenesis, cell migration, hypoxia response, and cholesterol biosynthesis. Intriguingly, type I interferon response was transiently activated, presumably forming an immuno-metabolic circuit with cholesterol metabolism. Neither global nor DEG-proximal changes were evident in (hydroxy)methylation. These results would not only provide a unique data resource for atherosclerosis research but present a potentially useful approach in transcriptome data interpretation.

Keywords

• Smooth muscle cell
• Cholesterol
• Epigenetics
• Inflammation
• Dedifferentiation