Department of Chemistry, Zhongshan Hospital, and Minhang Hospital, Fudan University, Shanghai 200000, China.
Anal Chem. 2024 Sep 10;96(36):14621-14629. doi: 10.1021/acs.analchem.4c03260. Epub 2024 Aug 27.
Macrophage-derived foam cells play a crucial role in plaque formation and rupture during the progression of atherosclerosis. Traditional studies have often overlooked the heterogeneity of foam cells, focusing instead on populations of cells. To address this, we have developed time-resolved, single-cell metabolomics and lipidomics approaches to explore the heterogeneity of macrophages during foam cell formation. Our dynamic metabolomic and lipidomic analyses revealed a dual regulatory axis involving inflammation and ferroptosis. Further, single-cell metabolomics and lipidomics have delineated a continuum of macrophage states, with varied susceptibilities to apoptosis and ferroptosis. Single-cell transcriptomic profiling confirmed these divergent fates, both in established cell lines and in macrophages derived from peripheral blood monocytes. This research has uncovered the complex molecular interactions that dictate these divergent cell fates, providing crucial insights into the pathogenesis of atherosclerosis.
巨噬细胞源性泡沫细胞在动脉粥样硬化进展过程中斑块的形成和破裂中起着至关重要的作用。传统的研究往往忽略了泡沫细胞的异质性，而是关注细胞群体。为了解决这个问题，我们开发了时间分辨的单细胞代谢组学和脂质组学方法来探索泡沫细胞形成过程中巨噬细胞的异质性。我们的动态代谢组学和脂质组学分析揭示了一个涉及炎症和铁死亡的双重调节轴。此外，单细胞代谢组学和脂质组学描绘了一个巨噬细胞状态的连续体，对细胞凋亡和铁死亡的敏感性不同。单细胞转录组学分析证实了这些不同的命运，无论是在已建立的细胞系中，还是在外周血单核细胞衍生的巨噬细胞中。这项研究揭示了决定这些不同细胞命运的复杂分子相互作用，为动脉粥样硬化的发病机制提供了重要的见解。
