Integrative single-cell and spatial transcriptome analysis reveals the functions of TREM2

This study employs an integrative approach combining single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and bulk RNA sequencing to investigate the complex cellular and molecular dynamics following myocardial infarction (MI). Quality control, batch correction, dimensionality reduction, clustering, and annotation were performed on scRNA and ST data. The Milo tool was used to analyze differential cell abundance. Developmental trajectory inference was conducted using the Monocle2 algorithm, and cell-cell communication was explored using CellPhoneDB and NicheNet. SCENIC analysis identified active transcription factors (TFs) in macrophage subtypes. Additionally, deconvolution was used to assess the spatial distribution of cell types. The functional roles of different myocardial regions were explored through cell communication patterns. Mouse MI and ischemia-reperfusion (I/R) models were established by ligating the left anterior descending (LAD) coronary artery. Molecular changes were analyzed using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence. In vitro, AC16 cardiomyocytes (CMs) and THP-1-derived M2 macrophages were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and co-culture experiments to study TREM2-mediated effects. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry, respectively. The study identified dynamic changes in the proportions of immune cell types at different time points post-MI. ST revealed distinct immune cell infiltration patterns in the infarct, border, and remote zones, with macrophages progressively infiltrating the infarct region over time. Functional enrichment analysis highlighted key pathways involved in inflammation, cell proliferation, and extracellular matrix remodeling across different cardiac regions. The study also identified Trem2