Single-cell multiomic analysis identifies macrophage subpopulations in promoting cardiac repair

Our study comprehensively investigated the epigenetic features of cardiac F4/80+CD45+ macrophages at 3 and 7 days after P1 and P10 MI at infarct, border, and remote zones of mouse hearts through single cell H3K27ac ChIP-seq. we identified 9 subclusters and analyzed their potential functions, cluster-specific enhancer features, and enrichment of cell-type specific transcription factors. Surprisingly, we found intracluster epigenetic heterogeneity exists with biological functions. Moreover, we identified two MI-responsive lineages and targeted one inflammatory lineage exhibiting obvious pre-regenerative function. Overall design: We performed single-cell RNA-seq on CD45+F4/80+ macrophages/monocytes isolated from the IZ and BZ of P10-Sham_Vehicle, P10-MI_Vehicle, and P10-MI_SB225002 hearts at 3 days after P10-MI. The heart tissues were manually divided into three zones (infarct zone, border zone and remote zone) and then digested with collagenase type II enzyme at 37°C for 30 min to generate single-cell suspensions. F4/80/CD45+ cardiac macrophages in infarct zone and border zone were collected and subjected to FACS sorting for CD45+/F4/80+ cells.