Cell Stem Cell: Regeneration requires specialized hepatic vascular recognition factor

Weill Cornell Medicine researchers have discovered a key protein that induces this program to build specialized liver blood vessels

There are many types of blood vessels in the human body, and they function differently from each other

In the study, published March 31 in the journal Cell Stem Cell, the researchers identified a protein called c-mafa -- a member of a class of transcription factor proteins that control a large number of genes - Necessary for the specific maturation of primitive endothelial cells into hepatic sinusoidal vessels

"These findings will set the stage for preclinical trials in which permanently damaged blood vessels can be replaced with healthy, engineered liver sinusoidal cells to accelerate regeneration and repair

At least millions of American adults are affected by chronic liver disease each year, and about 50,000 people die from chronic liver disease each year, according to the US Centers for Disease Control and Prevention

"Advanced liver disease and liver fibrosis are currently incurable unless a liver transplant is performed, an expensive and surgically challenging option that is not suitable for all patients and is often not timely due to a lack of suitable donor livers.

Previous studies have shown that liver sinusoidal and other vascular endothelial cells can help the organ resist fibrosis and even partially regenerate after injury

In the new study, the researchers tracked the gene activity of tens of thousands of individual endothelial cells in embryonic and neonatal mouse livers, showing how different types of liver endothelial cells emerge from immature progenitor cells

"This comprehensive analysis revealed that the transcription factor c-Maf is a key switch that controls the maturation and development of liver sinusoidal endothelial cells, making them highly unique blood vessels to support the daily needs and functions of liver cells

In contrast, forcing the human version of c-Maf to become active in unspecialized human endothelial cells caused these cells to develop unique markers of liver sinusoidal endothelial cells

The researchers are continuing to study how these potentially therapeutic cells develop in the liver and how best to induce them to build liver tissue in the lab

article title

Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction