Single-Cell Omics Analysis Reveals Critical Cell Subtypes and their Functional Attributes in Myocardial Ischemia-Reperfusion Injury

Abstract

Cardiac cell death and myocardial fibrosis after ischemia-reperfusion (I/R) injury are the primary causes of impaired cardiac function. Despite advances in therapies targeting ischemia, fibrosis, and angiogenesis, the early molecular and cellular mechanisms driving I/R injury remain poorly defined, particularly regarding interactions between specific cardiomyocyte (CM) subtypes and stromal cells. Extensive signaling interactions have been demonstrated between myocardial cells and fibroblasts during injury repair and remodeling, but the dynamic characteristics and molecular pathways involved in early I/R stages remain to be fully elucidated. Herein, we used single-cell transcriptomics to identify a key subtype of CMs, termed C0 Atcayos⁺ CMs, that are activated in I/R. Components of the Bmp6–(Bmpr1a+Bmpr2) and Fgf1–Fgfr1 signaling axes were highly expressed and mediated interactions between the C0 Atcayos⁺ CM subtype and fibroblasts. These pathways are known to promote angiogenesis and regulate endothelial homeostasis, and to be crucial in inhibiting myocardial fibrosis. Ligand-receptor interaction network visualization suggested that communication between C0 Atcayos⁺ CMs and fibroblasts might be a critical link in the transition from myocardial cell death to fibrosis after I/R. Targeting these signaling axes might therefore offer new strategies to impede fibrosis progression and improve cardiac function after I/R. This research provides a potential reference for inhibiting the progression of diseases such as myocardial fibrosis after I/R.

Keywords

Cardiomyocytes / ischemia/reperfusion / myocardial fibrosis / scRNA-seq / transcriptional regulatory

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