First Genetic Atlas of Healthy Human Liver Reveals Eight Functional Regions and Fatty Disease Vulnerability

Weizmann Institute scientists map the human liver in 2-micron resolution, revealing eight functional zones and new insights into fatty liver disease.

By: AXL Media

Published: May 1, 2026, 6:43 AM EDT

Source: Information for this report was sourced from EurekAlert!

Mapping the Microscopic Architecture of the Human Body’s Largest Organ

A collaborative research effort has produced the first high-resolution genetic atlas of a healthy human liver, revealing a complex internal organization that significantly differs from other mammals. By utilizing single-cell sequencing and precise spatial mapping, researchers identified over 500 simultaneous functions performed by hexagonal units known as lobules. This study, published in Nature, challenges decades of biological assumptions by demonstrating that human liver cells divide labor across eight distinct regions rather than the three coarse zones identified in the 1970s.

Altruistic Living Donation Provides Critical Path to Healthy Tissue

Historically, a comprehensive functional map of the human liver remained elusive due to the difficulty of obtaining healthy tissue samples. To overcome this, Professor Shalev Itzkovitz’s group at the Weizmann Institute of Science partnered with the Sheba Medical Center and the Mayo Clinic to source samples from altruistic living donors. Because the liver possesses an extraordinary capacity for regeneration, these healthy individuals were able to contribute tissue that allowed for the construction of a gene expression atlas at a resolution of 2 microns.

Distinct Evolution of Metabolic Activity in the Human Lobule Core

The research team performed comparative mapping across mice, pigs, and cows to identify evolutionary differences in liver function. In most mammals, cellular activity decreases toward the center of the lobule where oxygen and nutrients are scarce. However, the study found that the human lobule core remains highly active, performing critical tasks such as fat synthesis, glucose production during fasting, and toxin filtration. According to Itzkovitz, this suggests that the human liver evolved unique metabolic roles for resource-depleted areas that are not seen in other species.