Dysregulated RNA splicing induces regeneration failure in alcohol-associated liver disease

Individuals with progressive liver failure due to alcohol-related liver disease (ALD) are at a high mortality risk without liver transplantation. However, our understanding of derailed regenerative responses in ALD is limited. Here, we performed comprehensive multi-omic profiling of healthy and diseased human livers using single nucleus RNA- plus ATAC-seq. We report that hepatic immune milieu alterations prevent hepatocytes from transitioning to a proliferative progenitor-like state, trapping them in a non-functional intermediate state. Overall design: 10X multi-omics platform based profiling of human livers to obtain matched sn-RNAseq and sn-ATACseq profiles from fresh frozen livers of normal individuals, and SAH and AC patients