biostudies-literatureUnknown7(8)Meng Z<h4>Background & aims</h4>Cellular heterogeneity of innate immune cells, such as macrophages, in the liver is a hallmark of metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis. However, the mechanisms shaping liver macrophage heterogeneity and function during disease progression remain poorly understood.<h4>Methods</h4>Control or myeloid-specific <i>Tgfbr1</i> knockout mice (n = 9-12 per group) were fed a 12-week choline-deficient, amino acid-defined high-fat diet (CDA-HFD) or a 20-week GAN diet (40% fat, 22% fructose, 2% cholesterol). Liver tissue was analyzed using histopathology, quantitative PCR, immunoblotting, flow cytometry, and RNA sequencing (RNA-seq). Bulk RNA-seq (n = 3 per group) and single-nucleus RNA-seq were performed to investigate transcriptional reprogramJHEP reports : innovation in hepatology101488https://www.ebi.ac.uk/biostudies/studies/S-EPMC12284356biostudies-literatureMyeloid TGF-β signaling shapes liver macrophage heterogeneity and metabolic liver disease pathogenesis.PMC12284356Lee YTZhou LQiu XLin JDLi SChen ZLu YGallagher KALevi BMeng ZLiu TfalseMyeloid TGF-β signaling shapes liver macrophage heterogeneity and metabolic liver disease pathogenesis.<h4>Background & aims</h4>Cellular heterogeneity of innate immune cells, such as macrophages, in the liver is a hallmark of metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis. However, the mechanisms shaping liver macrophage heterogeneity and function during disease progression remain poorly understood.<h4>Methods</h4>Control or myeloid-specific <i>Tgfbr1</i> knockout mice (n = 9-12 per group) were fed a 12-week choline-deficient, amino acid-defined high-fat diet (CDA-HFD) or a 20-week GAN diet (40% fat, 22% fructose, 2% cholesterol). Liver tissue was analyzed using histopathology, quantitative PCR, immunoblotting, flow cytometry, and RNA sequencing (RNA-seq). Bulk RNA-seq (n = 3 per group) and single-nucleus RNA-seq were performed to investigate transcriptional reprogram2025-01-01T00:00:00Z2025 Aug2026-03-16T04:08:17.116Z2025-08-14T03:05:50.92ZS-EPMC122843564070406710.1016/j.jhepr.2025.101488