Dysregulated RNA splicing impairs regeneration in alcohol-associated liver disease.

ABSTRACT: Individuals with progressive liver failure risk dying without liver transplantation. However, our understanding of why regenerative responses are disrupted in failing livers is limited. Here, we perform multiomic profiling of healthy and diseased human livers using bulk and single-nucleus RNA- and ATAC-seq. We report that in alcohol-associated liver disease, alterations in the hepatic immune milieu prevent hepatocytes from transitioning to proliferative progenitors. We also find differences in RNA binding protein expression, particularly of the ESRP, PTBP, and SR families, leading to misregulation of developmentally controlled RNA splicing. Our data pinpoint ESRP2 as a disease-sensitive splicing factor and support a causal role for its deficiency in the pathogenesis of severe alcoholic hep

SUBMITTER: Chembazhi UV 

PROVIDER: S-EPMC12423296 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature