Single-cell spatial reconstruction reveals global division of labour in the mammalian liver.
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.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Keren Bahar
KB
Halpern
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Rom
R
Shenhav
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Orit
O
Matcovitch-Natan
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Beata
B
Toth
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Doron
D
Lemze
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Matan
M
Golan
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Efi E
EE
Massasa
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shaked
S
Baydatch
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shanie
S
Landen
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Andreas E
AE
Moor
Biological Services, Weizmann Institute of Science, Rehovot, Israel.
Alexander
A
Brandis
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Amir
A
Giladi
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Avigail Stokar
AS
Avihail
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Eyal
E
David
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Ido
I
Amit
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Shalev
S
Itzkovitz
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D020869:Gene Expression Profiling; D016678:Genome / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017423:Sequence Analysis, RNA; D000072760:Single Molecule Imaging; D059010:Single-Cell Analysis; D059467:Transcriptome / Q000235:genetics
D001647:Bile Acids and Salts