Dynamic activation and dual roles of SOX9+ hepatocytes in liver regeneration under acute and chronic injury by single-cell transcriptomics

Background: hepatocytes during acute and chronic liver injury using integrated single-cell transcriptomics. Methods: Publicly available single-cell RNA sequencing (scRNA-seq) datasets derived from mouse liver models of partial hepatectomy (PHx) and acetaminophen-induced acute liver injury (APAP), as well as human liver tissues with nonalcoholic fatty liver disease (NAFLD), were analyzed. Data were processed using Seurat and Harmony for batch correction. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA). Results: hepatocytes progressively expand and acquire transcriptional programs associated with inflammatory signaling and wound-healing processes. Conclusion: hepatocytes as a dynamic and context-dependent hepatocyte subpopulation associated with adaptive metabolic responses during regeneration and altered inflammatory and wound-healing-related programs under chronic injury.