In a groundbreaking study published in the prestigious journal Cell Stem Cell, researchers from National Yang Ming Chiao Tung University (NYCU) and Harvard University have identified a critical gene that functions as a molecular “brake”—suppressing the liver’s innate ability to regenerate damaged tissue. The discovery may pave the way for innovative treatments in regenerative medicine, particularly for liver diseases with limited therapeutic options.
Turning Metabolic Cells into Repair Agents
The human liver is one of the few organs capable of self-repair. Among its regenerative feats is the ability to heal damaged bile ducts by reprogramming liver cells—originally responsible for metabolism—into bile duct epithelial cells. While this transformation is remarkable, the underlying molecular switch that enables or limits this ability has remained poorly understood.
Scientists have pinpointed a gene called HBO1 that prevents liver cells from making this identity shift. As a genetic brake, HBO1 blocks the reprogramming process, halting the transformation into bile duct cells. According to the research team, targeting HBO1 could unlock new possibilities for enhancing liver cell plasticity, potentially accelerating tissue repair and regeneration.
“HBO1 is recruited by the transcriptional co-activator YAP to specific DNA sites, where it epigenetically suppresses the genes required for cellular reprogramming,” explained Dr. Wei-Chien Yuan, Assistant Professor at NYCU’s Department of Life Sciences and Institute of Genome Sciences (DLSIGS). “Inhibiting HBO1 could remove this brake, enabling faster chromatin remodeling and boosting the conversion of liver cells into functional bile duct epithelial cells.”
The study highlights a new layer of epigenetic regulation in organ regeneration. By modulating this regulatory axis, future therapies could enhance the body’s natural healing capacity—offering hope to patients suffering from bile duct injuries and chronic liver conditions.
Building on this discovery, the NYCU-Harvard team is now conducting preclinical studies to translate the findings into therapeutic strategies to bring liver regeneration closer to clinical reality.
Source : NYCU NEWS
