What happens in the liver

Scientists from the Weizmann Institute discovered that the different layers of the liver units perform different functions, which allows the liver to make optimal use of its resources.

If a person wakes up in the morning with a clear head and a lot of energy, it is a sign that his liver is working well. The liver produces the sugar (glucose), which is necessary for body and brain activity, at times when this "fuel" does not come from food, such as, for example, after sleep and before breakfast. In addition, the liver produces proteins, cleanses the body of toxins, stores substances, and performs many other essential functions. In the study thatRecently published in the scientific journal Nature Weizmann Institute of Science scientists have shown that the liver's wonderful ability to perform all these functions at the same time can be attributed, among other things, to the division of work between its cells.

The liver is made up of tiny hexagonal units ("vessels"), each of which contains layers like an onion. Dr. Shalu Itzkowitz, and his research group in the Department of Molecular Biology of the Cell at the Weizmann Institute of Science, mapped the gene activity in all the cells of the liver vessel, and discovered that the different layers perform different actions. "Apparently, the spatial (and layered) division allows the liver to make optimal use of the available resources," says Dr. Itzkovitz. "We found that it is possible to divide the liver cells into at least nine layers, and each of them specializes in its own roles."

This is how the scientists found that the production of glucose, of substances for blood clotting, and of many other substances takes place in the outer layers of the liver vessel. "These layers are rich in oxygen, so they allow the construction of ATP molecules, the basic fuel necessary for the production of these substances." On the other hand, in the inner layers of the ship, completely different processes are carried out: here the toxins and other substances intended for decomposition are broken down, and in the intermediate layers the hormone hepcidin, which controls the levels of iron in the blood, is created, and more. The scientists also discovered that certain processes, such as bile production, are carried out across several layers, in a kind of "production line".

All this was discovered thanks to the atlas of gene expression in the liver, which the scientists prepared. This is the first atlas of its kind for this body part. For its preparation, the scientists combined two innovative technologies. In the first step, in collaboration with Prof. Ido Amit from the Institute's Department of Immunology, they deciphered the genome of 1,500 individual liver cells, and found the expression patterns of approximately 20 genes in each cell. This action was based on measuring levels of messenger RNA molecules, which contain genetic instructions for protein construction. In this way, the scientists got a complete picture of the gene expression in each cell, but not the location of the cells. Therefore, at the same time, they used another method, in the development of which Dr. Itzkowitz participated in the past: observation of individual molecules of messenger RNA using a fluorescence microscope, which gives the scientists information about the location of the cells in which the messenger RNA was observed. An algorithm developed by the scientists crossed the two technologies, and received information regarding gene expression, in precise locations. Thus they discovered that more Half of the 7,000 genes expressed in the liver act differently in cells located in different areas.

This in-depth analysis of gene expression may help in the study of common liver diseases, such as liver cancer or fatty liver, and it may also pave the way for similar mapping of cell activity in other organs.

The research group included the post-doctoral researchers Dr. Keren Bahar Halpern, Dr. Beata Tut-Cohen, Dr. Doron Lamza and Dr. Anders Mor, and the research students Rom Shanhav, Matan Golan, Efi Massa, Shaked Bidetz, Shani Landan and Abigail Stoker of the Department of Molecular Cell Biology; and Orit Matkovits-Nathan, Amir Giladi and Eyal David from the laboratory of Prof. Ido Amit in the Department of Immunology, as well as staff scientist Dr. Alexander Brandis fromThe Life Sciences Research Infrastructure Unit.

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The human liver is built as a beehive of about 100,000 tiny hexagonal-shaped units ("hepacles").