Groundbreaking study by Israeli researchers create first map of healthy human liver

A team of Israeli scientists at the Weizmann Institute of Science have conducted the first study that presents a healthy human liver map.

The groundbreaking study was carried out in cooperation with the Sheba Medical Center outside Tel Aviv and the world-renowned Mayo Clinic in Rochester, Minnesota.

In addition to producing an accurate genetic atlas of a healthy human liver, the innovative study also provides deeper insight into the functions of the liver and why disease targets specific areas. 

The study unveiled that the functions in the human liver differ from those of other mammals. 

Dr. Oran Yakubovsky, a senior general surgery resident at Sheba Medical Center and a Weizmann Institute doctoral student, emphasized the liver’s central role in the human body. 

“The liver is the largest internal organ in the human body, and it is responsible for many functions,” Yakubovsky stated. 

“The liver is responsible for the body’s metabolic activity, heat production, protein production, the coagulation system and filtering toxins – it knows how to take drugs and toxins from the blood, change their form and remove them from the body. It is also responsible for the body’s sugar regulation together with the pancreas,” he explained.

“The liver is built from very small functional units called lobules,” Yakubovsky continued. 

“Blood flows from the digestive system into the liver and enters the lobule, which looks like a hexagon, through small blood vessels located around its perimeter. From there it flows inward to the center, and from there it flows to the rest of the body. Inside this lobule, all the actions of liver cells on the blood are actually carried out,” the senior general surgeon assessed.

New technologies have enabled scientists to map the organ in greater detail. 

“Until just a few years ago, to characterize what a cell does, you had to look at it under a microscope, stain it, see what it responds to and how it behaves. But since the Human Genome Project, there are advanced methods that allow us to read genetic material in the cell called RNA,” Yakubovsky explained.

“That allows us to characterize it at a deeper level — what proteins are there, what it knows how to do. That sequencing really brought about a revolution. If we once thought that every liver cell performs the same functions, today we can say that there are many types of cells doing different jobs depending on their location within the lobule,” he continued. 

Prof. Shalev Itzkovitz from the Weizmann Institute’s Department of Molecular Cell Biology revealed that the scientific team discovered thousands of specialized genes in different locations of the liver.

“Thousands of genes were found to be active at different levels in liver cells in different locations, indicating a far more precise and complex internal organization than we had thought,” Itzkovitz said.

The professor said the findings mark a significant shift in how scientists understand the liver’s internal structure and disease patterns.

“Instead of the rough division into three activity zones, which has been accepted for decades, the atlas revealed eight regions with distinct roles. The precise mapping of the liver now allows any laboratory in the world to dive deep into the liver and study why different regions are vulnerable to different diseases. Metabolic diseases, for example, tend to begin at the center of the lobule, while viral and autoimmune inflammations appear mainly at its edges. Liver cancer and metastases from other cancers also have their preferred locations. The key to understanding why this is the case lies in the precise genetic information we collected,” the professor explained.

He added that the detailed genetic mapping could help researchers better understand how and where diseases originate, potentially improving targeted treatments in the future.

“Based on the precise mapping of the liver, it will be possible in the future to develop treatments focused on the genes that cause a certain region to be especially vulnerable to a specific disease,” he explained. 

“Moreover, the model of building a genetic atlas at single-cell resolution from samples of healthy donors can be applied to additional organs that until now have not been precisely mapped in humans, and it may fundamentally change the way we understand the structure and function of the human body,” Itzkovitz added.