Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce cardiomyocyte injury
Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce cardiomyocyte injury
复制标题
心脏免疫细胞的单细胞转录组分析表明，Rel 驱动的 CD72 阳性巨噬细胞可诱导心肌细胞损伤。
DOI：
10.1093/cvr/cvab193
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发表时间：
2021-07-09
影响因子：
10.8
通讯作者：
Lu, Lu
中科院分区：
文献类型：
--
作者：
Ni, Shi-Hao;Xu, Jin-Dong;Lu, Lu
目的是我们研究的目的是通过单细胞测序研究具有横向主动脉收缩（TAC）的小鼠心脏巨噬细胞（CM PHI）的异质性，并确定与心脏损伤相关的巨噬细胞的子集。方法和结果我们使用单细胞mRNA测序数据从CD45+细胞中选择了所有CM Phi。通过降低尺寸，聚类和富集分析，CD72（HI）CM Phi被确定为促炎性巨噬细胞的子集。伪时间轨迹和CHIP-seq分析被确定为诱导CD72（HI）CM PHI分化的关键转录因子。 REL KD和RER - / - 骨髓嵌合小鼠遭受TAC的小鼠显示出缓解心脏损伤的特征，包括降低的细胞因子和ROS水平，禁止心肌细胞死亡。在TAC模型中，养育相反表达的单核细胞和CD72（HI）CM PHI注射直接加剧了心脏损伤。 CD72（HI）巨噬细胞还发挥了与心肌梗塞相关的促炎和心脏损伤作用。在人类中，心力衰竭患者在扩张心肌病和缺血性心肌病后表现出CD72（HI）CM PHI水平升高。结论骨髓衍生的，介导的CD72（HI）巨噬细胞起着促炎作用，诱导心脏损伤，因此可以作为多种心血管疾病的治疗靶标。
Aims The goal of our study was to investigate the heterogeneity of cardiac macrophages (CM phi s) in mice with transverse aortic constriction (TAC) via single-cell sequencing and identify a subset of macrophages associated with heart injury. Methods and results We selected all CM phi s from CD45+ cells using single-cell mRNA sequencing data. Through dimension reduction, clustering, and enrichment analyses, CD72(hi) CM phi s were identified as a subset of pro-inflammatory macrophages. The pseudo-time trajectory and ChIP-Seq analyses identified Rel as the key transcription factor that induces CD72(hi) CM phi differentiation. Rel KD and Rel-/- bone marrow chimaera mice subjected to TAC showed features of mitigated cardiac injury, including decreased levels of cytokines and ROS, which prohibited cardiomyocyte death. The transfer of adoptive Rel-overexpressing monocytes and CD72(hi) CM phi injection directly aggravated heart injury in the TAC model. The CD72(hi) macrophages also exerted pro-inflammatory and cardiac injury effects associated with myocardial infarction. In humans, patients with heart failure exhibit increased CD72(hi) CM phi levels following dilated cardiomyopathy and ischaemic cardiomyopathy. Conclusion Bone marrow-derived, Rel-mediated CD72(hi) macrophages play a pro-inflammatory role, induce cardiac injury and, thus, may serve as a therapeutic target for multiple cardiovascular diseases.