Weizmann and Sheba scientists map the healthy human liver in unprecedented detail

Researchers at the Weizmann Institute of Science and Sheba Medical Center published a detailed spatial map of the healthy human liver in Nature on 15 April 2026. The study, led by Dr. Oran Yakubovsky in the lab of Prof. Shalev Itzkovitz, records which genes are switched on in individual liver cells and exactly where those cells sit inside the organ, at a resolution of about two microns.

Healthy human liver tissue is hard to obtain, because most samples come from people who are ill or who have died. The team solved this by working with Sheba's transplant surgeons and using small samples from living donors, whose livers regrow after part is given away. They compared the human data with healthy livers from mice, pigs and cows, collaborating with colleagues at the Mayo Clinic and the University of Freiburg.

The atlas overturns a textbook picture. For decades the basic functional unit of the liver, the lobule, was described as having three zones. The new map divides its labour into eight distinct regions, with thousands of genes varying by position. It also shows that humans differ from other mammals: in people, the centre of the lobule handles many demanding jobs, including making fat, producing glucose during fasting, filtering toxins and secreting bile, and even the liver's resident immune cells tend to cluster there.

That concentration of work may come at a price. When the researchers examined cells that had started to store fat, they saw the cells try to protect themselves by switching off fat production and switching on fat breakdown, while losing some of the mitochondrial machinery needed to finish the job. Itzkovitz noted that metabolic diseases tend to begin in the centre of the lobule, and that the liver's efficient design was not built for a modern diet heavy in fats and carbohydrates.