Single-Cell RNA Sequencing Reveals the Temporal Diversity and Dynamics of Cardiac Immunity after Myocardial Infarction
Single-Cell RNA Sequencing Reveals the Temporal Diversity and Dynamics of Cardiac Immunity after Myocardial Infarction
复制标题
单细胞 RNA 测序揭示心肌梗塞后心脏免疫的时间多样性和动态
DOI：
10.1002/smtd.202100752
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发表时间：
2022-01-13
期刊：
影响因子：
12.4
通讯作者：
Fan, Xiaohui
中科院分区：
文献类型：
--
作者：
Jin, Kaiyu;Gao, Shan;Fan, Xiaohui
心肌梗死（MI）与心脏免疫的时间调节密切相关。然而，由于缺乏MI后免疫调节/抗炎靶点，目前各种临床试验都失败了。在小鼠左前降支冠状动脉结扎模型中，在损伤后0、3、7和14天对心脏Cd 45（+）免疫细胞进行单细胞RNA测序分析。确定了主要的免疫细胞群体、不同的子集和动态变化。巨噬细胞（M空集）最丰富，在梗死后3d达到高峰。Mempty set-5和Mempty set-6是该时间点的主要浸润子集，具有强的炎症因子表达。进一步的分析表明，抑制这些集合通过防止随后的白细胞外渗和不良重塑来减弱病理性MI进展。还分别在第7天和第14天检测到大量凋亡中性粒细胞和促纤维化巨噬细胞亚群。这些结果为开发MI中细胞类型和时间特异性干预提供了基础。
Myocardial infarction (MI) is strongly associated with the temporal regulation of cardiac immunity. However, a variety of current clinical trials have failed because of the lack of post-MI immunomodulating/anti-inflammatory targets. Single-cell RNA sequencing analysis of the cardiac Cd45(+) immune cell at 0, 3, 7, and 14 d after injury in a mouse left anterior descending coronary artery ligation model is performed. Major immune cell populations, distinct subsets, and dynamic changes are identified. Macrophages (Mempty set) are most abundant, peaking at 3 d after infarction. Mempty set-5 and Mempty set-6 are the predominant infiltrated subsets at this time point, with strong expression of inflammatory factors. Further analysis demonstrates that suppressing these sets attenuated pathological MI progression by preventing subsequent leukocyte extravasation and adverse remodeling. Abundant apoptotic neutrophils and a profibrotic macrophage subset on days 7 and 14, respectively, are also detected. These results provide a basis for developing cell type- and time-specific interventions in MI.