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A liver cell atlas to help understand how cells change, during liver disease development & progression

Liver diseases are one of the biggest health problems in the world and a leading cause of death. It is important to know the various functions of individual liver cells so that new treatment algorithms can be developed.  

Modern scientific methods are now available to do just that. Using sophisticated practices, scientists from the Max Planck Institute of Immuno-biology and Epigenetics in Freiburg and the University of Strasbourg, Germany have been able to present a comprehensive liver cell atlas. They have been able to create a detailed map of the cell populations in the healthy human liver, which can be used as a reference point against the development of liver diseases.

Max Planck Group Leader Dominic Grün in cooperation with the Baumert Lab have used a technique called single-cell RNA sequencing to capture the different cell types and cell states at very high resolution and to understand how they change during development or upon disease progression.

The data comes from the analysis of 10000 cells from nine human donors. The cell atlas maps all important liver cell types, including hepatocytes, the major metabolic cells of the liver, endothelial cells lining the blood vessels, liver resident macrophages and other immune cell types, as well as bile duct cells and liver epithelial progenitors, which aid in the unique regeneration of the organ.

In addition, the researchers also discovered that there is an astonishing diversity among individual cells of the alleged same cell type. These new subtypes of hepatocytes, endothelial cells, and macrophages, which, although look alike, have different individual gene expression profiles.

Single cell RNA sequencing is capable of exploring individual cells, which are isolated and sequenced separately. The sequencing is used to determine how many messenger RNA molecules (mRNA) of each gene are present in the cell.

Dr. Dominic Grün explained that, “The messenger RNA transmits the blueprints stored in the DNA to the protein factories. By measuring which RNA molecules are present in a cell at a certain point in time, we can identify which genes are active. This gives us a kind of fingerprint that provides us with a comprehensive insight into the very nature of each cell. This enables us to understand which functions the cell performs, how it is regulated and also what happens when diseases develop.”

Dr. Nadim Aizarani further explained that their discovery of novel properties of a subpopulation of bile duct cells that are precursor cells or progenitors are able to form organoids, like stem cells, and have the capacity to develop into different cell types to form hepatocytes or bile duct cells when they were cultivated in the lab. Thus, these cells had the potential to healthy liver regeneration tissue and could also be involved in the development of liver diseases or tumors.

The ability of single-cell sequencing to capture the molecular signature of each healthy or diseased cell in the sample to be examined may help to develop improved treatment options in the future.

The Freiburg and Strasbourg researchers see their latest study findings of the human liver cell atlas to become an essential reference database at the molecular level for liver diseases and especially liver cancer research.