Scientists Create Detailed Atlas of Liver Cells

In a paper published today in Nature, researchers present a comprehensive cell atlas of the human liver created using single-cell RNA sequencing techniques. The atlas maps all important liver cell types, giving an unprecedentedly detailed view of the diversity of cell types and cell states and how they change during development or disease progression.

The liver is necessary for a wide range of essential bodily functions, playing significant roles in nutritional processing, metabolism, and detoxifying blood. Liver diseases are one of the biggest health problems worldwide; these include fatty liver disease, liver cancer, or hepatitis. To better treat these diseases, it is important to gain deeper understanding of the liver and liver disease states.

To do this, scientists from the Max Planck Institute of Immunobiology and Epigenetics collected 1000 cells from nine human donors. Using computational single-cell analysis methods and tailor-made algorithms, they were able to map the molecular signature of each healthy or diseased cell in the sample, allowing them to characterize each type in detail and compare healthy and diseased states. By contrast, traditional methods, such as tumor tissue analysis, provide an average value, losing the contribution of rare cells that may be of paramount importance in disease development.

The scientists discovered a high level of diversity among individual cells of the same cell type. They discovered new subtypes of hepatocytes, endothelial cells, and macrophages, which appear morphologically the same, but have discrete gene expression profiles.

The team also identified a previously unknown property of bile duct cells, which transport bile to the gallbladder. Their data indicates that these cells are progenitors. These progenitor cells were able to either differentiate into hepatocytes or bile duct cells in culture. The researchers believe these cells play an important role in liver regeneration and could be important in development of liver disease or tumors.

The researchers are confident that their cell atlas of the human liver will prove a powerful tool to advance research and understanding of liver disease on the molecular level and possibly create new treatments.

Image: Single cells were isolated from liver tissue derived from 9 different patients to perform single-cell RNA-sequencing. After applying computational single-cell analysis methods, a human liver cell atlas, or cell type map, was established, enabling the identification of previously unknown sub-types (depicted as clusters represented by numbers on the map). We discovered rare sub-types of bile duct cells in the liver, which include a population of liver epithelial progenitors that can give rise to organoids capable of developing into hepatocytes or bile duct cells. Image courtesy of MPI of Immunobiology and Epigenetics, Freiburg, Grün.