A spatial map of human liver cirrhosis reveals the patho-architecture and gene signatures associated with cell state transitions during liver disease - Spatial Transcriptomics (10X Visium)

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 from hepatocytes to cholangiocytes associated with disease remodelling.We identifypro-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 providesa spatial atlas of gene regulation and defines molecular signatures associated liver diseasefor targeted therapeutics or as early diagnostic markers of progressive liver disease. This is the 10X Visium data for the work.