biostudies-literatureUnknownRobarts DRNIA NIH HHSNCRR NIH HHSNIDDK NIH HHSNIGMS NIH HHSNIH HHS<h4>Background & aims</h4>O-GlcNAcylation is a post-translational modification catalyzed by the enzyme O-GlcNAc transferase (OGT), which transfers a single N-acetylglucosamine sugar from UDP-GlcNAc to the protein on serine and threonine residues on proteins. Another enzyme, O-GlcNAcase (OGA), removes this modification. O-GlcNAcylation plays an important role in pathophysiology. Here, we report that O-GlcNAcylation is essential for hepatocyte differentiation, and chronic loss results in fibrosis and hepatocellular carcinoma.<h4>Methods</h4>Single-cell RNA-sequencing was used to investigate hepatocyte differentiation in hepatocyte-specific OGT-KO mice with increased hepatic O-GlcNAcylation and in OGA-KO mice with decreased O-GlcNAcylation in hepatocytes. HCC patient samples and the DEN-inducbioRxiv : the preprint server for biology2023.02.16.528884https://www.ebi.ac.uk/biostudies/studies/S-EPMC9949138biostudies-literatureThe Essential Role of O-GlcNAcylation in Hepatic Differentiation.PMC9949138P30 GM122731P30 GM118247R01 AG064227P20 RR021940P20 GM144269S10 OD021743R56 DK112768Slawson CHanover JAZachara NEPaine-Cabrera DRobarts DRVenneman KKKotulkar MApte UfalseThe Essential Role of O-GlcNAcylation in Hepatic Differentiation.<h4>Background & aims</h4>O-GlcNAcylation is a post-translational modification catalyzed by the enzyme O-GlcNAc transferase (OGT), which transfers a single N-acetylglucosamine sugar from UDP-GlcNAc to the protein on serine and threonine residues on proteins. Another enzyme, O-GlcNAcase (OGA), removes this modification. O-GlcNAcylation plays an important role in pathophysiology. Here, we report that O-GlcNAcylation is essential for hepatocyte differentiation, and chronic loss results in fibrosis and hepatocellular carcinoma.<h4>Methods</h4>Single-cell RNA-sequencing was used to investigate hepatocyte differentiation in hepatocyte-specific OGT-KO mice with increased hepatic O-GlcNAcylation and in OGA-KO mice with decreased O-GlcNAcylation in hepatocytes. HCC patient samples and the DEN-induc2023-01-01T00:00:00Z2023 Feb2026-04-08T12:26:53.299Z2025-04-05T21:08:20.585ZS-EPMC99491383682491710.1101/2023.02.16.528884