Single-cell multi-omics reveals cellular atlases and cell–cell interaction networks in metabolic dysfunction-associated steatotic liver disease (MASLD)

Objective To summarize recent advances in single-cell multi-omics technologies in metabolic dysfunction-associated steatotic liver disease (MASLD), with a focus on cellular atlases, cellular heterogeneity, and intercellular communication networks in hepatic and extrahepatic tissues. Methods This narrative review synthesizes findings from studies identified primarily through PubMed searches supplemented by manual curation of reference lists. Search terms included “single-cell,” “spatial transcriptomics,” “MASLD,” “NAFLD,” “NASH,” “MASH,” “steatohepatitis,” and “liver fibrosis.” Studies applying single-cell transcriptomics, single-nucleus RNA sequencing, spatial transcriptomics, single-cell eQTL analysis, and integrative multi-omics approaches were included. The last literature search was conducted in July 2026. Results: Single-cell technologies have revealed key cellular alterations during MASLD progression, including disrupted hepatocyte metabolic zonation, heterogeneous activation states of hepatic stellate cells, macrophage functional reprogramming, immune cell dysfunction, and dynamic remodeling of the hepatic microenvironment. Spatial transcriptomics has further resolved the spatial organization of these cellular changes, whereas single-cell eQTL analyses have linked genetic susceptibility loci to cell-specific regulatory programs. Single-cell profiling of intestinal, adipose, and vascular tissues has expanded the understanding of extrahepatic contributions and gut–liver communication in MASLD. These advances provide a foundation for drug target identification, mechanistic understanding of current and investigational therapies, and assessment of treatment response at cellular resolution. Conclusion Single-cell multi-omics is transforming MASLD research from tissue-level characterization toward cellular-resolution understanding, providing novel insights into disease stratification, therapeutic target discovery, and biomarker development, and advancing precision hepatology.