Time-series transcriptome profiling of liver regeneration in ALLPS models of mice identifies the Cyp8b1 as a potential target for hepatocyte proliferation.

Liver regeneration is a complex and highly orchestrated process essential for maintaining hepatic function after injury or surgical resection. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is an innovative surgical strategy that induces rapid and robust liver regeneration, significantly increasing future liver remnant (FLR) volume within a short period. However, the molecular mechanisms underlying ALPPS-driven regeneration remain poorly understood. Here, we performed time-series transcriptomic profiling of murine liver tissues at multiple time points after ALPPS to elucidate key regulators of hepatocyte proliferation. We identified significant temporal changes in gene expression. Intersection analysis of DEGs across sequential time points revealed one consistently downregulated gene, Cyp8b1, and four consistently upregulated genes. Cyp8b1, which exhibited the highest expression among these, was significantly downregulated during regeneration. Functional in vitro experiments in AML12 hepatocytes demonstrated that Cyp8b1 knockdown enhanced cell viability, promoted proliferation and upregulated the expression of key cell cycle genes. These results suggest that Cyp8b1 serves as a negative regulator of hepatocyte proliferation and a potential therapeutic target for enhancing liver regeneration after ALPPS and other liver resection procedures.