Breakthrough Discovery: New Liver Cell Type May Combat Severe Liver Disease, Study Finds

Scientists have uncovered a previously unknown type of liver cell that may offer protection against metabolic dysfunction-associated steatohepatitis (MASH), a severe form of liver disease, according to a new study published in the Journal of Clinical Investigation.

MASH, which affects between 5% and 10% of the U.S. adult population, can progress to cirrhosis and liver cancer. The disease is part of a broader category known as metabolic dysfunction-associated steatotic liver disease (MASLD).

The liver contains more than a dozen distinct cell types, including hepatocytes (liver cells), stromal cells, and immune cells. Researchers at the University of Michigan Life Sciences Institute, led by faculty member Jiandie Lin, study how these cells communicate to maintain liver health and how these interactions change in disease.

Identifying a New Liver Cell Type

The team analyzed gene expression patterns in individual hepatocytes from both healthy and MASH-affected liver samples. Their goal was to pinpoint specific cell types that could indicate disease risk.

“Traditionally, hepatocytes are divided into three zones based on location-specific gene expression patterns tailored to specialized functions. What was surprising was that, in addition to these three groups, we identified a new cluster of cells with a unique identity. This particular group only appeared in MASH-affected livers.”

Jiandie Lin, professor of cell and developmental biology and senior author of the study, explained.

A key characteristic of these newly discovered cells was the presence of cellular senescence—a state in which cells stop dividing but do not die. Senescent cells can disrupt normal tissue function, promote harmful inflammation, and contribute to disease progression.

The Role of the Themis Gene

Further investigation revealed unusual activity in a gene called Themis. Typically, Themis is expressed in immune cells called T cells but is inactive in healthy hepatocytes. However, in both mouse and human MASH livers, Themis expression was significantly elevated.

“In both mouse and human MASH liver, Themis expression was strongly increased. It ranked as one of the top genes being activated. The next question is: Is this increased THEMIS damaging the liver, or is the cell activating this pathway to help adapt to metabolic stress in MASH?”

To determine the impact of THEMIS, researchers compared liver health in normal mice with that of genetically modified mice lacking Themis in their hepatocytes. The livers without THEMIS showed worse outcomes, including increased liver injury, senescence, inflammation, and fibrosis.

Conversely, when THEMIS levels were artificially increased in hepatocytes, the team observed reduced senescence and improved protection against liver injury and MASH.

Implications for Future Treatments

“It’s pretty exciting because only a couple of other studies have identified this cell population, and not much was known about what these cells are doing in disease,” said Xiaoxue Qiu, lead author of the study and a former researcher in Lin’s lab who has since established her own research group.

The findings suggest that THEMIS and the newly identified liver cell type could serve as targets for developing therapies to treat or prevent MASH and related liver diseases.