Single-cell multi-omics reveals cellular atlases and cell–cell interaction networks in metabolic dysfunction-associated steatotic liver disease (MASLD)
Abstract
ObjectiveTo 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.MethodsThis 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.ConclusionSingle-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.
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BibTeX
@article{dou2026singlecell,
title = {{Single-cell multi-omics reveals cellular atlases and cell–cell interaction networks in metabolic dysfunction-associated steatotic liver disease (MASLD)}},
author = {Linshuang Dou and Wenying Qi and Jinyu Li and Yanbao Tian and Yizi Ao and Shuying Hu and Xiaoke Li},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1941671},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1941671},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell multi-omics reveals cellular atlases and cell–cell interaction networks in metabolic dysfunction-associated steatotic liver disease (MASLD)
AU - Linshuang Dou
AU - Wenying Qi
AU - Jinyu Li
AU - Yanbao Tian
AU - Yizi Ao
AU - Shuying Hu
AU - Xiaoke Li
PY - 2026
DA - 2026/11/06
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1941671
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1941671
AB - ObjectiveTo 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.MethodsThis 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.ConclusionSingle-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.
SN - 1663-9812
ER -