Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts

Seung Hyun Jung, Byung Hee Hwang, Sun Shin, Eun Hye Park, Sin Hee Park, Chan Woo Kim, Eunmin Kim, Eunho Choo, Ik Jun Choi, Filip K. Swirski, Kiyuk Chang, Yeun Jun Chung

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41 Scopus citations

Abstract

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.

Original languageEnglish
Article number4580
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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