Zooming in on Liver Zonation

Abstract

The liver is composed of approximately a million hepatic lobules, microscopic hexagonal units that are patterned together in a three dimensional vasculature. Blood filters from portal triad points into central vein points at the center of each hexagonal lobule (Fig. 1). The lobule consists of hepatocyte plates that carry a gradient of recently absorbed nutrients from the digestive tract, diminishing oxygen, and hormones and Wnt morphogens to form different metabolic zones that the hepatocytes occupy. This specialized structure partitions hepatic functions such as liver detoxification, dietary nutrient absorption, and lipid synthesis (1). While a large body of knowledge on zonation has been obtained in the last decade, the resolution of zonal differences was limited to three zones: periportal, transitional, and perivenous.Genes that exhibit zonation can be expressed in a gradient or restricted to a specific zone, and can be either stable or dynamically expressed depending on nutrition, oxygen, morphogens, hormones, and circadian rhythm (1). The Shalev Itzkovitz laboratory at the Weizmann Institute of Science in Rehovot, Israel, refined this categorization by investigating murine liver lobule zonation with a combination of two cutting-edge single-cell resolution technologies, single-molecule fluorescence in situ hybridization (smFISH) and single cell RNA sequencing (scRNA-seq). Their findings yielded spatial genome-wide high-resolution gene expression profiles across liver lobules as described in the letter Bahar Halpern K, Shenhav R, Matcovitch-Natan O et al. Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature 2017;542 (7641):352-356. This article is protected by copyright. All rights reserved.

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