Acquisition of epithelial plasticity in human chronic liver disease. (

These scientists wanted to understand how the liver can regenerate itself when it is injured or diseased. They studied liver samples from 47 patients with a type of liver disease called metabolic dysfunction-associated steatotic liver disease. They used a special technique called single-nucleus RNA sequencing to look at the individual cells in the liver and create a map of how they change during the progression of the disease.

They also used advanced 3D imaging to see how the structure of the liver changes during the disease. They found that the liver cells, called hepatocytes, lose their normal organization and the bile duct system in the liver undergoes significant changes. What was most surprising is that they discovered that some liver cells could change into a different type of cell, called cholangiocytes, without the need for stem cells or other specialized cells.

The scientists then did more tests to confirm their findings, and they found that a specific pathway in the liver cells, called the PI3K-AKT-mTOR pathway, plays a key role in this cell transformation process, which is linked to insulin signaling in the body. This discovery could help develop new treatments for chronic diseases by understanding how the liver and other organs can change and repair themselves.

Gribben C., Galanakis V., Calderwood A., Williams EC., Chazarra-Gil R., Larraz M., Frau C., Puengel T., Guillot A., Rouhani FJ., Mahbubani K., Godfrey E., Davies SE., Athanasiadis E., Saeb-Parsy K., Tacke F., Allison M., Mohorianu I., Vallier L. Acquisition of epithelial plasticity in human chronic liver disease. Nature. 2024 May 22. doi: 10.1038/s41586-024-07465-2.

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