Single-cell profiling identifies a pathogenic Msx2⁺ VSMC subpopulation underlying aortic arch-specific vascular calcification

This study investigates why the aortic arch is more prone to calcification than the descending aorta. Vascular calcification is a serious condition with no effective treatment, where blood vessel cells become similar to bone-forming cells. We used single-cell RNA sequencing on a mouse model of vitamin D-induced calcification to compare these two aortic regions. Our key discovery was a specific subpopulation of Msx2-positive vascular smooth muscle cells that is uniquely found in the aortic arch and appears to drive its increased calcification. This finding provides new insights into the cellular basis of regional calcification differences and could lead to new therapeutic targets.本研究旨在探究主动脉弓相较于降主动脉更易发生钙化的原因。血管钙化是一种尚无有效治疗手段的严重病症，患病时血管细胞会向成骨细胞样细胞转化。我们采用维生素D诱导钙化的小鼠模型，对这两处主动脉区域开展单细胞RNA测序（single-cell RNA sequencing）分析以进行对比。本研究的核心发现为：存在一类特异性表达Msx2的血管平滑肌细胞亚群，该亚群仅存在于主动脉弓中，且似乎是驱动该区域钙化程度升高的关键因素。这一发现为阐明区域间钙化差异的细胞基础提供了全新视角，同时有望催生全新的治疗靶点。