Scientists Map the Hidden Architecture of the Human Liver

Jerusalem, 7 May, 2026 (TPS-IL) -- In a breakthrough that could reshape scientists’ understanding of liver disease, Israeli researchers have created the first ultra-high-resolution genetic atlas of the healthy human liver — revealing that the organ is organized very differently in humans than in laboratory animals.

Scientists at the Weizmann Institute of Science, working with colleagues at Sheba Medical Center and Germany’s Freiburg University, mapped gene activity inside healthy human liver tissue at a resolution of just two microns — thinner than a spider’s silk. The achievement is being described as the first detailed “genetic atlas” of the human liver, allowing scientists to pinpoint exactly which genes are active in specific parts of the organ.

Researchers say the findings, which were published in the peer-reviewed Nature, may help explain why modern humans are especially vulnerable to metabolic fatty liver disease, which affects roughly one in four adults worldwide.

Fatty liver disease is a condition in which excess fat builds up inside liver cells. The liver normally contains only small amounts of fat, but when fat makes up more than about 5–10% of its weight, it’s considered fatty liver disease. If left untreated, it can worsen over time, leading to liver inflammation, scarring, and potentially liver failure. It is treated with weight loss, diet, exercise, and control of blood sugar and cholesterol.

For decades, scientists believed the liver was divided into roughly three functional zones. The new atlas revealed eight highly specialized regions, each carrying out different tasks. Even more strikingly, researchers discovered that the human liver behaves differently from the livers of mice and other mammals commonly used in medical research.

“Thousands of genes were found to be active at different levels in liver cells in different locations, indicating a much more precise and complex internal organization than we had thought,” said Prof. Shalev Itzkovich of the Weizmann Institute, who led the study.

A High-Resolution Map of the Human Liver

The liver, the body’s largest internal organ, performs more than 500 functions simultaneously, including filtering toxins, regulating blood sugar, producing bile for digestion, and storing energy.

Scientists have long known these functions are divided among tiny hexagonal structures called lobules. In most mammals, cells located at the center of these lobules are relatively inactive because they receive blood that has already been depleted of oxygen and nutrients.

Humans, however, appear to function differently.

The study found that the center of the human liver remains highly active, performing energy-intensive functions such as fat production, glucose generation during fasting, toxin filtration, and bile production.

Researchers say this unique organization may help explain why humans are particularly prone to obesity-related liver disease.

“This division of labor is both a blessing and a curse,” Itzkovich said. “It allows our liver to store carbohydrates efficiently. But this efficient division of labor was not designed for the modern diet, which is rich in fats and carbohydrates, and may explain why we tend to accumulate excess fat in the liver and suffer from scarring.”

The project depended on tissue samples from healthy liver donors — a rare opportunity because healthy liver tissue is difficult to obtain for research. The liver’s unusual ability to regenerate allows living donors to donate portions of the organ during transplant procedures.

Researchers also uncovered what may be a uniquely human defense mechanism. Specialized immune cells known as Kupffer cells were concentrated in the center of liver lobules rather than at the edges, where they are typically found in other mammals.

“We hypothesize that they have ‘moved to the center’ in humans to cope with the increased erosion,” said Dr. Oren Yakubovsky, a lead author of the study and a physician at Sheba Medical Center.

The team then used the atlas to study metabolic fatty liver disease, now the most common liver disorder in the Western world. They found that liver cells initially try to protect themselves from fat accumulation by activating fat-breaking genes and suppressing fat-production genes.

But the researchers also identified a biological weakness: accumulating fat damages mitochondria, the structures inside cells responsible for processing fats efficiently.

Scientists say the atlas could eventually help doctors develop treatments targeting specific vulnerable regions of the liver.

“Based on the precise mapping of the liver, it will be possible in the future to develop therapies that target genes that make a particular region particularly vulnerable to a specific disease,” Itzkovich said.