Single-cell spatial reconstruction reveals global division of labor in the mammalian liver

By K. B. Halpern, Rom Shenhav, Orit Matcovitch-Natan, Beáta Tóth, D. Lemze, Matan Golan, Efi E. Massasa, Shaked Baydatch, S. Landen, A. Moor and 6 more. Nature, 2017

885 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Hepatology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8dbbcc7bb3afd663f929837e1ca127bc7bbdbec4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

Qing Nie

In Molecular Biology

Citations in the corpus

Inferring spatial and signaling relationships between cells from single cell transcriptomic data (2020, methodology): “Posterior probability estimates were carried out on spatial data described by a mixture model 13 or simpli ﬁ ed to one-dimensional bins 14 to assign spatial origins to individual cells.”
Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology (2017, background): “As a result, hepatocytes receive their characteristic zonal alignment along the sinusoids, which has beenmapped at single-cell resolution to reveal that around 50% of liver genes are nonuniformly expressed, in line with this zonation (115).”