GEO series

GeoMx GeoMx-DSP Toxic Lipid-induced Epigenetic Activation of ICAM1 in Liver Sinusoidal Endothelium Regulates Myeloid-Driven Fibro-inflammatory Response in MASH

GSE309979 Homo sapiens Other 217 samples Submitted 2026/08/05 Platform GPL30173

Summary

Background: Liver sinusoidal endothelial cells (LSECs) acquire a proinflammatory phenotype in metabolic dysfunction-associated steatohepatitis (MASH), characterized by elevated adhesion molecules and inflammatory mediators—a process termed lipotoxic endotheliopathy. However, the molecular drivers of this transformation remain incompletely defined. Methods: We employed complementary models of lipotoxicity and MASH, including palmitate-treated primary human LSECs (in vitro), cultured precision-cut liver slices from normal human and mice liver with MASH-inducing media as well as MASH mice (ex vivo), and diet-induced MASH models (in vivo). Results: GeoMx digital spatial profiling of human MASH livers revealed enriched proinflammatory and fibrogenic signaling between LSECs and myeloid cells. Among the top upregulated genes and ligand-receptor pairs was ICAM1, whose expression correlated with disease severity and was increased in human MASH by immunostaining. ATAC-seq on primary mouse LSECs showed enhanced chromatin accessibility at the Icam1 promoter in MASH. Chromatin immunoprecipitation confirmed enrichment of the active epigenetic mark H3K27ac and BRD4 binding at the ICAM1 promoter in human LSECs under lipotoxic stress. Mechanistically, we identified the GSK3β/c-Jun/BRD4 axis as a key regulator of ICAM1 induction in LSECs. In vivo, ICAM1-neutralizing antibody or endothelial-specific epigenetic suppression reduced hepatic inflammation, injury, and fibrosis in MASH mice. Conclusion: ICAM1 is epigenetically upregulated in LSECs during lipotoxic stress and promotes myeloid cell recruitment in MASH. Targeting the epigenetic regulation of ICAM1 may offer a novel therapeutic strategy for treating human MASH.

Published in

Toxic lipid-induced epigenetic activation of ICAM1 in liver sinusoidal endothelium regulates myeloid-driven fibro-inflammatory response in MASH

Guo Q, Satthawiwat N, Sano A et al. · Hepatology (Baltimore, Md.) 2026 · PMID 41983905 · doi:10.1097/HEP.0000000000001742

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Direct links to NCBI, no account and no request form: the whole study as GSE309979_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 217 samples.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗

Also filed as BioProject PRJNA1364859. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41983905) ↗

Study design

8 conditions, mostly in triplicate

GeoMx-DSP-1001660010639-D-G ×8 GeoMx-DSP-1001660010639-D-E ×7 GeoMx-DSP-1001660010639-D-F ×7 GeoMx-DSP-1001660010639-D-H ×5 GeoMx-DSP-1001660010639-D-D ×4 GeoMx-DSP-1001660010639-D-A ×3 GeoMx-DSP-1001660010639-D-B ×3 GeoMx-DSP-1001660010639-D-C ×3

Supports a between-group comparison across 40 samples.

8 replicated groups read from the first 40 of 217 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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