A spatial map of human liver cirrhosis reveals the patho-architecture and gene signatures associated with cell state transitions during liver disease - single nuclei RNA-seq
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 snRNA-seq data for the work.