Spatial sorting enables comprehensive characterization of liver zonation

被引：124

作者：

Ben-Moshe, Shani ^{[1
]}

Shapira, Yonatan ^{[1
]}

Moor, Andreas E. ^{[1
,2
]}

Manco, Rita ^{[1
]}

Veg, Tamar ^{[1
]}

Halpern, Keren Bahar ^{[1
]}

Itzkovitz, Shalev ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Cell Biol, Rehovot, Israel

[2] Univ Zurich, Inst Mol Canc Res, Zurich, Switzerland

来源：

NATURE METABOLISM | 2019年 / 1卷 / 09期

基金：

以色列科学基金会; 欧洲研究理事会;

关键词：

GENE-EXPRESSION; CIRCULATING MICRORNAS; CATENIN; CELLS; TRANSCRIPTION; BIOMARKERS; REVEALS; OVEREXPRESSION; IDENTIFICATION; REGENERATION;

D O I：

10.1038/s42255-019-0109-9

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The mammalian liver is composed of repeating hexagonal units termed lobules. Spatially resolved single-cell transcriptomics has revealed that about half of hepatocyte genes are differentially expressed across the lobule, yet technical limitations have impeded reconstructing similar global spatial maps of other hepatocyte features. Here, we show how zonated surface markers can be used to sort hepatocytes from defined lobule zones with high spatial resolution. We apply transcriptomics, microRNA (miRNA) array measurements and mass spectrometry proteomics to reconstruct spatial atlases of multiple zonated features. We demonstrate that protein zonation largely overlaps with messenger RNA zonation, with the periportal HNF4a as an exception. We identify zonation of miRNAs, such as miR-122, and inverse zonation of miRNAs and their hepatocyte target genes, highlighting potential regulation of gene expression levels through zonated mRNA degradation. Among the targets, we find the pericentral Wingless-related integration site (Wnt) receptors Fzd7 and Fzd8 and the periportal Wnt inhibitors Tcf7l1 and Ctnnbip1. Our approach facilitates reconstructing spatial atlases of multiple cellular features in the liver and other structured tissues.

引用

页码：899 / 911

页数：13

共 78 条

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