A Journey to the Center of the Liver: A first genetic atlas of a healthy human liver at a resolution of 2 microns

Amazing stuff!

"... In a new study ... present the first genetic atlas of a healthy human liver at a resolution of 2 microns. The findings show that the division of labor in the human liver differs from that of other mammals and is more extensive than previously recognized, helping explain why certain regions of the liver are particularly vulnerable to fatty liver disease. ...

the liver has a remarkable capacity for regeneration, healthy individuals can donate a substantial portion of their livers to patients in need. ..."

From the abstract:

"Reconstructing gene expression atlases for human tissues is challenging due to limited access to healthy samples from live individuals.

Neurologically deceased donors often show ischaemic changes, and tissues near diseased regions may have altered gene expression. The liver, with its unique regenerative capacity, allows analysis from live healthy donors.

Here, using spatial transcriptomics (Visium, Visium HD3, multiplexed error-robust fluorescence in situ hybridization (MERFISH)4 and PhenoCycler imaging) and single-nucleus RNA sequencing, we analysed 16 liver samples: 8 from young live healthy donors and 8 from individuals with liver pathology, sampling ‘adjacent normal’ tissue.

Livers from live healthy donors displayed significant gene expression differences compared with the adjacent normal tissues from individuals with liver pathology.

Hepatocytes and non-parenchymal cells exhibited marked zonation along the porto–central axis of the liver lobules, with key functions being pericentrally shifted compared to mice and other mammals.

Our atlas identified dynamic programmes in early steatotic hepatocytes, including a decline in nuclear-encoded mitochondrial proteins and a compensatory increase in mitochondria-encoded transcripts.

This study presents a spatial gene expression reference for the healthy human liver and insights into hepatocyte changes in early steatosis."

A Journey to the Center of the Liver - Life Sciences | Weizmann Wonder Wander - News, Features and Discoveries "A first-of-its-kind genetic atlas reveals how human liver cells divide their labor – and why some regions are especially vulnerable to fatty liver disease"

A spatial atlas of the healthy human liver from live donors (open access)

Fig. 1: A spatial expression atlas of human and mammalian livers.

Fig. 2: Zonation of hepatocyte gene expression.