Liver Zonation | ScienceGate

The distribution of complementary metabolic functions in hepatocytes along a portocentral axis is called liver zonation. Endothelial secreted Wnt ligands maintain metabolic zonation in the adult murine liver but whether those ligands are necessary to initiate zonation in the immature liver has been only partially explored. Also, numerous non-metabolic proteins display zonated expression in the adult liver but it is not entirely clear if their localization requires endothelial Wnts. Here we used a novel transgenic mouse model to compare the spatial distribution of zonated non-metabolic proteins with that of typical zonated metabolic enzymes during liver maturation and after acute injury induced by carbon tetrachloride (CCl4). We also investigated how preventing Wnt ligand secretion from endothelial cells affects zonation patterns under homeostasis and after acute injury. Our study demonstrates that metabolic and non-metabolic zonation are established non-synchronously during maturation and regeneration and require multiple endothelial Wnt sources.

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Liver Zonation – Revisiting Old Questions With New Technologies

Frontiers in Physiology ◽

10.3389/fphys.2021.732929 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rory P. Cunningham ◽

Natalie Porat-Shliom

Keyword(s):

Liver Disease ◽

Spatial Organization ◽

New Technologies ◽

Single Cell Analysis ◽

Normal Liver ◽

Alcoholic Fatty Liver ◽

Liver Zonation ◽

Hepatocyte Heterogeneity ◽

Glucose And Lipid Homeostasis ◽

Technological Limitations

Despite the ever-increasing prevalence of non-alcoholic fatty liver disease (NAFLD), the etiology and pathogenesis remain poorly understood. This is due, in part, to the liver’s complex physiology and architecture. The liver maintains glucose and lipid homeostasis by coordinating numerous metabolic processes with great efficiency. This is made possible by the spatial compartmentalization of metabolic pathways a phenomenon known as liver zonation. Despite the importance of zonation to normal liver function, it is unresolved if and how perturbations to liver zonation can drive hepatic pathophysiology and NAFLD development. While hepatocyte heterogeneity has been identified over a century ago, its examination had been severely hindered due to technological limitations. Recent advances in single cell analysis and imaging technologies now permit further characterization of cells across the liver lobule. This review summarizes the advances in examining liver zonation and elucidating its regulatory role in liver physiology and pathology. Understanding the spatial organization of metabolism is vital to further our knowledge of liver disease and to provide targeted therapeutic avenues.

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Investigation of the hepatic respiration and liver zonation on rat hepatocytes using an integrated oxygen biosensor in a microscale device

Biotechnology Progress ◽

10.1002/btpr.2854 ◽

2019 ◽

Vol 35 (5) ◽

Cited By ~ 3

Author(s):

Satomi Matsumoto ◽

Astia R. Safitri ◽

Mathieu Danoy ◽

Toshiro Maekawa ◽

Haruyuki Kinoshita ◽

...

Keyword(s):

Rat Hepatocytes ◽

Liver Zonation

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Characterization of liver zonation‐like transcriptomic patterns in HLCs derived from hiPSCs in a microfluidic biochip environment

Biotechnology Progress ◽

10.1002/btpr.3013 ◽

2020 ◽

Vol 36 (5) ◽

Author(s):

Mathieu Danoy ◽

Stéphane Poulain ◽

Myriam Lereau‐Bernier ◽

Sachi Kato ◽

Benedikt Scheidecker ◽

...

Keyword(s):

Liver Zonation

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