SaptioTemporal dynamics of macrophage heterogeneity after myocardial infarction
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE165857 | GEO | 2022/06/19
REPOSITORIES: GEO
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Project description:In this study, we attempted to identify the heterogeneity and temporal dynamics of leukocytes at single-cell level in mouse heart after inducing MI using the longitudinal single-cell RNA sequencing and spatial transcriptome sequencing.
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Project description:Background: The onset, progression, and outcomes of myocardial infarction (MI), a serious issue worldwide, are regulated by inflammatory responses. Numerous studies have demonstrated the complexity and importance of post-infarction immunity. Nonetheless, little is known about dynamic changes in cell type and function during disease progression. Methods: Single-cell RNA sequencing (scRNA-seq) was used to map the Cd45+ immune cell composition at different time points (0, 3, 7 and 14 days) after MI within a mouse left anterior descending coronary artery (LAD) ligation model. A time course-analysis was performed to characterize dynamic changes in cell populations. Multiparameter flow cytometry, immunohistochemistry, and immunofluorescence were performed using the same mouse model. Results: Major immune cell populations, distinct subsets, and dynamic changes were identified. Macrophages (Mø)/monocytes were most abundant, peaking at 3 days after infarction. Mø-5 and Mø-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. Conclusions: Our results provide a basis for developing cell type- and time-specific interventions in MI.
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