Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Nat Commun. 2022 Aug 6;13(1):4580. doi: 10.1038/s41467-022-32284-2.
Heart failure (HF) is a frequent consequence of myocardial infarction (MI). Identification of the precise, time-dependent composition of inflammatory cells may provide clues for the establishment of new biomarkers and therapeutic approaches targeting post-MI HF. Here, we investigate the spatiotemporal dynamics of MI-associated immune cells in a mouse model of MI using spatial transcriptomics and single-cell RNA-sequencing (scRNA-seq). We identify twelve major immune cell populations; their proportions dynamically change after MI. Macrophages are the most abundant population at all-time points (>60%), except for day 1 post-MI. Trajectory inference analysis shows upregulation of Trem2 expression in macrophages during the late phase post-MI. In vivo injection of soluble Trem2 leads to significant functional and structural improvements in infarcted hearts. Our data contribute to a better understanding of MI-driven immune responses and further investigation to determine the regulatory factors of the Trem2 signaling pathway will aid the development of novel therapeutic strategies for post-MI HF.
心力衰竭（HF）是心肌梗死（MI）的常见后果。鉴定炎症细胞的确切、时相关组成可能为针对 MI 后 HF 的新型生物标志物和治疗方法的建立提供线索。在这里，我们使用空间转录组学和单细胞 RNA 测序（scRNA-seq）在 MI 小鼠模型中研究 MI 相关免疫细胞的时空动态。我们鉴定了 12 种主要的免疫细胞群；它们的比例在 MI 后会动态变化。巨噬细胞在所有时间点（>60%）都是最丰富的群体，除了 MI 后第 1 天。轨迹推断分析显示，Trem2 在 MI 后晚期在巨噬细胞中表达上调。体内注射可溶性 Trem2 可导致梗死心脏的功能和结构显著改善。我们的数据有助于更好地理解 MI 驱动的免疫反应，进一步研究确定 Trem2 信号通路的调节因子将有助于为 MI 后 HF 开发新的治疗策略。
