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解析和可视化心脏巨噬细胞的功能多样性。

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages.

机构信息

Division of Cardiology, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine (M.H., M.C., K.J.L.).

Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (J.L., A.W., S.E.).

出版信息

Circ Res. 2024 Jun 7;134(12):1791-1807. doi: 10.1161/CIRCRESAHA.124.323817. Epub 2024 Jun 6.

Abstract

Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.

摘要

心肌巨噬细胞是一类功能多样化的细胞群体,参与心脏的稳态、修复和重塑。随着单细胞技术的最新进展,根据转录特征和细胞表面蛋白表达,可以阐明特定的巨噬细胞亚群,从而深入了解心脏中巨噬细胞的多样性。命运图谱技术和联体动物研究为巨噬细胞的发生和动力学提供了深入了解,确定了源自胚胎和成人定型造血祖细胞的亚群,分别包括组织驻留和骨髓单核细胞衍生的巨噬细胞。在心脏中,这些亚群在稳态和疾病状态下具有不同的组织龛位和功能作用,心脏驻留巨噬细胞是一种保护性细胞群体,而骨髓单核细胞衍生的心脏巨噬细胞具有上下文依赖性效应,既触发促炎组织损伤,又促进修复功能。随着对心脏巨噬细胞亚群临床相关性的认识不断增加,人们越来越需要在活体动物和患者中检测和测量心脏巨噬细胞的组成。与正电子发射断层扫描/计算机断层扫描和正电子发射断层扫描/磁共振成像兼容的新型分子示踪剂使研究人员能够非侵入性和连续地在心脏内可视化心脏巨噬细胞亚群,以确定与疾病的关联并测量治疗反应。如今,这一蓬勃发展领域的进展有望推动临床转化的新时代。

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