Inoue Kentaro, Araki Hiromitsu, Miura Fumihito, Ito Takashi
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Biochem Biophys Rep. 2021 Jun 27;27:101061. doi: 10.1016/j.bbrep.2021.101061. eCollection 2021 Sep.
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.
源自血管平滑肌细胞（SMC）的巨噬细胞样细胞在动脉粥样硬化形成中起关键作用，并且DNA羟甲基化与转分化有关。我们研究了胆固醇诱导的转分化过程中人类冠状动脉SMC的转录组和（羟）甲基化组。一种独特的方法是先详尽鉴定差异表达基因，然后以基因本体为中心进行聚类，这有助于更深入地理解参与细胞外基质组织、血管生成、细胞迁移、缺氧反应和胆固醇生物合成的基因的多方面调控。有趣的是，I型干扰素反应被短暂激活，推测与胆固醇代谢形成了一个免疫代谢回路。（羟）甲基化方面，无论是整体还是差异表达基因近端的变化都不明显。这些结果不仅将为动脉粥样硬化研究提供独特的数据资源，还为转录组数据解读提供了一种潜在有用的方法。
