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[This article belongs to Volume - 70, Issue - 3]
Published on : 2025-03-20 14:14:48
Article Code: AMJ-20-03-2025-12314
Title : Single-Cell Multi-Omic Analysis Reveals a Transitional Hepatocyte State Driving Liver Regeneration After Acetaminophen-Induced Necrosis
Author(s) : Dr. Ana Silva, Dr. Kenji Sato, Dr. Emily Thompson
Abstract :
The cellular heterogeneity underlying liver regeneration remains incompletely understood. Employing single-cell
RNA-seq, ATAC-seq, and mitochondrial DNA mutational profiling of 45,000 cells from acetaminophen-overdosed
murine livers, we identified a rare transitional hepatocyte population (tHeps) expressing both mature hepatocyte
markers (Alb, Ttr) and biliary transcription factors (Sox9, Opgn). These tHeps emerged at 48 hours post-injury,
exhibited enhanced proliferative capacity, and gave rise to regenerating hepatocyte clones. Lineage-tracing using
Sox9-CreER mice confirmed their bipotent differentiation potential. Interleukin-6/STAT3 signaling was requisite for
tHep emergence. Therapeutic enhancement of this transitional state may accelerate recovery in acute liver failure.