Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
Keren Bahar-Halpern1, Rom Shenhav1, Ido Amit2 and Shalev Itzkovitz1
1Weizmann Institute of Science, Department of Molecular Cell Biology, Rehovot, Israel; 2Weizmann Institute of Science, Department of Immunology, Rehovot, Israel
The mammalian liver consists of hexagonal-shaped lobules, 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 labor has not been achieved. Here we measure the entire transcriptome of thousands of mouse liver cells and infer their lobule coordinates based on 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 about 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 reconstruction of similar spatial genomic blueprints for other mammalian organs.