New Liver Cell Type Discovered to Protect Against MASH

Researchers have identified a new type of liver cell that may provide critical insights into treating severe liver disease. According to a study published in the Journal of Clinical Investigation in May 2026, this specific cell population is linked to a signaling pathway that can protect the organ against metabolic dysfunction-associated steatohepatitis, known as MASH.

MASH is a severe manifestation of metabolic dysfunction-associated steatitis liver disease (MASLD). This condition affects between 5% and 10% of the adult population in the United States and can progress to cause liver cancer and cirrhosis.

The liver consists of more than a dozen different cell types, including immune cells, stromal cells, and liver cells called hepatocytes. Researchers in the laboratory of Jiandie Lin, a professor of cell and developmental biology and faculty member at the University of Michigan Life Sciences Institute, study how these cell types communicate to maintain health and how those interactions shift during the onset of disease.

Discovery of Disease-Associated Hepatocytes

In May 2026, the research team analyzed gene expression signatures from individual hepatocytes in liver samples from both healthy subjects and those with MASH. The goal was to identify specific cell types that might indicate a higher risk of disease.

Jiandie Lin noted that hepatocytes are typically categorized into three zones based on gene expression patterns that correspond to specialized functions. However, the data revealed a distinct cluster of cells that possessed a unique identity and appeared exclusively in livers affected by MASH.

These cells were distinguished by signatures of cellular senescence. Senescence is a state in which a cell stops dividing but does not die. In this arrested state, senescent cells can contribute to disease by increasing harmful inflammation and interfering with the normal function of the surrounding tissue.

The Role of the Themis Gene

Further analysis by the team revealed unusual activity from a gene called Themis, which encodes the protein THEMIS. While the Themis gene is typically active in T cells—a type of immune cell—it is normally inactive in healthy hepatocytes.

The researchers found that Themis expression was strongly increased in MASH livers in both humans and mice, ranking among the most activated genes in those samples.

To determine if this increase was harmful or a protective adaptation to metabolic stress, the team conducted experiments using mouse models. They compared the liver health of normal mice against mice where Themis was specifically deleted from the hepatocytes.

The results indicated that the absence of THEMIS led to significantly worse outcomes. Livers without the protein showed increased levels of:

• Liver injury
• Cellular senescence
• Inflammation
• Fibrosis

Conversely, when the researchers increased THEMIS levels in hepatocytes, they observed a decrease in senescence and improved protection against MASH and liver injury.

Therapeutic Implications

The findings suggest that Themis acts as a key regulator of hepatocyte senescence. This discovery provides a potential starting point for identifying other drivers of liver damage and exploring whether the THEMIS pathway can be used as a therapeutic target for patients with MASH.

Xiaoxue Qiu, the lead author of the study and a former researcher in the Lin lab who now leads her own laboratory at the University of Minnesota, highlighted the significance of the discovery.

It’s pretty exciting, because only a couple of other studies have identified this cell population, and not much was really known about what these cells are doing in disease. And now we are seeing that Themis is a key regulator of hepatocyte senescence and that manipulating this subtype of disease-associated hepatocytes can have a major impact on disease progression.Xiaoxue Qiu

The research included contributors from the University of Michigan and the University of Pittsburgh School of Medicine. The study was supported by the American Heart Association, the National Institutes of Health, and the UM Diabetes Research Center.

All procedures involving mice were conducted in accordance with institutional guidelines and were approved by the Institutional Animal Care and Use Committee at the University of Michigan.