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

Author

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  • Seung-Hyun Jung

    (The Catholic University of Korea
    The Catholic University of Korea)

  • Byung-Hee Hwang

    (The Catholic University of Korea
    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
    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
    The Catholic University of Korea)

  • Yeun-Jun Chung

    (The Catholic University of Korea
    The Catholic University of Korea
    The Catholic University of Korea)

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.

Suggested Citation

  • 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, 2022. "Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32284-2
    DOI: 10.1038/s41467-022-32284-2
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    References listed on IDEAS

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    1. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
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    3. Li Zhong & Ying Xu & Rengong Zhuo & Tingting Wang & Kai Wang & Ruizhi Huang & Daxin Wang & Yue Gao & Yifei Zhu & Xuan Sheng & Kai Chen & Na Wang & Lin Zhu & Dan Can & Yuka Marten & Mitsuru Shinohara &, 2019. "Author Correction: Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
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