SRP298022 PRJNA685594 GSE163246 DNA hydroxymethylation analysis for target regions in human smooth muscle cells. Macrophage-like cells derived from vascular smooth muscle cells (SMCs) play critical roles in atherogenesis, and TET2-mediated DNA hydroxymethylation was implicated to regulate the transdifferentiation. We examined transcriptomes and (hydroxy)methylomes of human coronary artery SMCs during cholesterol-induced transdifferentiation. A unique approach of gene ontology (GO)-centric clustering of differentially expressed genes exhaustively identified through all possible pairwise comparisons (pan-DEGs) revealed dynamic and multifaceted modulations of genes involved in extracellular matrix organization, angiogenesis, cell migration, hypoxia response, and cholesterol biosynthesis. Intriguingly, transient activation was observed for an immuno-metabolic circuit consisting of type I interferon response and cholesterol metabolism. We found neither global nor DEG-proximal change in (hydroxy)methylation. These datasets would serve as a unique resource to address the mechanisms underlying cholesterol-induced transdifferentiation of SMCs. Moreover, GO-centric clustering of pan-DEGs may provide a useful approach to interpret multifaceted transcriptomic alterations. Overall design: We conducted a series of genome and epigenome analysis, including RNA-sequencing and DNA methylation and hydroxymethylation status in human smooth muscle cells. GSE163246 pubmed 34258396 parent_bioproject PRJNA685416