Single-cell RNA Sequencing Reveals the Heterogeneity of Monocyte-derived Macrophages in Liver of Metabolic Dysfunction-associated Steatotic Liver Disease

However, current therapeutic strategies targeting macrophage-mediated inflammation have shown limited clinical efficacy in MASLD. Using single-cell RNA sequencing (scRNA-seq) analysis of liver-infiltrating MoMFs from MASLD mouse models, we identified seven distinct clusters (c0-c6) with unique molecular signatures.

Among these, the predominant CD14+CCR2+ (c0) showed multifaceted functions in fibrosis, lipid phagocytosis, and antigen presentation beyond inflammation. We identified two distinct clusters, CCR3+ (c3) and CCR7+ (c4) MoMFs, which exhibited enhanced pro-inflammatory/oxidative stress activity and specialized antigen-presenting capacity, respectively. Pseudotime analysis revealed that the resident basal cluster (c1) could give rise to both CD14+CCR2+ (c0) and CCR7+ (c4) MoMFs during disease progression, challenging the traditional view that CCR2+ MoMFs exclusively originate from bone marrow.