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 () and Yeun-Jun Chung ()
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Seung-Hyun Jung: The Catholic University of Korea
Byung-Hee Hwang: The Catholic University of Korea
Sun Shin: The Catholic University of Korea
Eun-Hye Park: The Catholic University of Korea
Sin-Hee Park: The Catholic University of Korea
Chan Woo Kim: The Catholic University of Korea
Eunmin Kim: The Catholic University of Korea
Eunho Choo: The Catholic University of Korea
Ik Jun Choi: The Catholic University of Korea
Filip K. Swirski: Icahn School of Medicine at Mount Sinai
Kiyuk Chang: The Catholic University of Korea
Yeun-Jun Chung: The Catholic University of Korea

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32284-2

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