Single-cell RNA Sequencing Reveals the Temporal Diversity and Dynamics of Cardiac Immunity after Myocardial Infarction

Abstract

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. We performed single-cell RNA sequencing analysis of cardiac Cd45+ immune cell at 0, 3, 7, and 14 days after injury in a mouse left anterior descending coronary artery ligation model. Major immune cell populations, distinct subsets, and dynamic changes were identified. Macrophages (Mo)/monocytes were most abundant, peaking at 3 days after infarction. Mo-5 and Mo-6 were the predominant infiltrated subsets at this time point, with strong expression of inflammatory factors. Further analysis demonstrated that suppressing these sets attenuated pathological MI progression by preventing subsequent leukocyte extravasation and adverse remodeling. We also detected abundant apoptotic neutrophils and a profibrotic macrophage subset on days 7 and 14 respectively. These results provide a basis for developing cell type- and time-specific interventions in MI. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/452902v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1d7c810org.highwire.dtl.DTLVardef@18f9c9dorg.highwire.dtl.DTLVardef@17325f7org.highwire.dtl.DTLVardef@c1a4e7_HPS_FORMAT_FIGEXP M_FIG C_FIG Temporal regulation of cardiac immunity is strongly associated with the onset, progression, and outcomes of MI. Our study of time-series scRNA-seq on the whole cardiac immune cells isolated from the LAD ligation mice and the tanshinone IIA treated mice shed light on the underlying pathology of MI.