Single-cell Spatial Reconstruction Reveals Global Division of Labour in the Mammalian Liver

Overview

Journal Nature

Specialty Science

Date 2017 Feb 7

PMID 28166538

Citations 461

Authors

Keren Bahar Halpern

Rom Shenhav

Orit Matcovitch-Natan

Beata Toth

Doron Lemze

Matan Golan

Efi E Massasa

Shaked Baydatch

Shanie Landen

Andreas E Moor

Alexander Brandis

Amir Giladi

Avigail Stokar Avihail

Eyal David

Ido Amit

Shalev Itzkovitz

Affiliations

Soon will be listed here.

Abstract

The mammalian liver consists of hexagon-shaped lobules that are radially polarized by blood flow and morphogens. Key liver genes have been shown to be differentially expressed along the lobule axis, a phenomenon termed zonation, but a detailed genome-wide reconstruction of this spatial division of labour has not been achieved. Here we measure the entire transcriptome of thousands of mouse liver cells and infer their lobule coordinates on the basis of a panel of zonated landmark genes, characterized with single-molecule fluorescence in situ hybridization. Using this approach, we obtain the zonation profiles of all liver genes with high spatial resolution. We find that around 50% of liver genes are significantly zonated and uncover abundant non-monotonic profiles that peak at the mid-lobule layers. These include a spatial order of bile acid biosynthesis enzymes that matches their position in the enzymatic cascade. Our approach can facilitate the reconstruction of similar spatial genomic blueprints for other mammalian organs.

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