ArticleEMBO molecular medicine2025
Spatial gene regulatory networks driving cell state transitions during human liver disease.
Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Matrix stiffness shapes early transcriptional trajectories during hepatic stellate cell activation.Hepatology international · 2026Article
- Embryonic Phase Transition/Separation on Hepatic Liquid Crystal Droplets Is Essential for Liver Development.Biology · 2026Article
- Shared mechanisms of organ fibrosis.JCI insight · 2026Review
- Epigenetic reprogramming of hepatic antigen presenting cells in chronic liver disease.Frontiers in immunology · 2026Review
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
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Authors and funding
21 authors.
Funding
Abstract
Liver fibrosis is a major cause of death worldwide. As a progressive step in chronic liver disease, fibrosis is almost always diagnosed too late with limited treatment options. Here, we uncover the spatial transcriptional landscape driving human liver fibrosis using single nuclei RNA and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to deconvolute multi-cell spatial transcriptomic profiling in human liver cirrhosis. Through multi-modal data integration, we define molecular signatures driving cell state transitions in liver disease and define an impaired cellular response and directional trajectory between hepatocytes and cholangiocytes associated with disease remodelling. We identify pro-fibrogenic signatures in non-parenchymal cell subpopulations co-localised within the fibrotic niche and localise transitional cell states at the scar interface. This combined approach provides a spatial atlas of gene regulation and defines molecular signatures associated with liver disease for targeted therapeutics or as early diagnostic markers of progressive liver disease.
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Registered trials
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