In vivo CRISPR screening reveals epigenetic regulators of hepatobiliary plasticity.

ABSTRACT: Following prolonged liver injury, a small fraction of hepatocytes undergoes reprogramming to become cholangiocytes or biliary epithelial cells (BECs). This physiological process involves chromatin and transcriptional remodeling, but the epigenetic mediators are largely unknown. Here, we exploited a lineage-traced model of liver injury to investigate the role of histone post-translational modification in biliary reprogramming. Using mass spectrometry, we defined the repertoire of histone marks that are globally altered in quantity during reprogramming. Next, applying an in vivo CRISPR screening approach, we identified seven histone-modifying enzymes that alter the efficiency of hepatobiliary reprogramming. Among these, the histone methyltransferase and demethylase Nsd1 and Kdm2a</

SUBMITTER: Sussman JH 

PROVIDER: S-EPMC12047657 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature