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Spatially Compact Arrangement of Larval Zebrafish Sections for Spatial Transcriptomic Analysis

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Shani Ben-Moshe¹, Yonatan Shapira¹, Andreas E Moor^1,2

¹Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Nature Metabolism

|September 20, 2019

Summary

Researchers mapped spatial features of liver cells using advanced techniques. This study reveals how gene and protein zonation in hepatocytes provides insights into liver function and potential disease mechanisms.

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Area of Science:

Hepatology and Molecular Biology
Spatial Transcriptomics and Proteomics
Cellular Zonation in Mammalian Liver

Background:

The liver lobule, a hexagonal unit, exhibits spatial heterogeneity in gene expression among hepatocytes.
Previous technical limitations hindered comprehensive spatial mapping of diverse hepatocyte features beyond gene expression.

Purpose of the Study:

To develop a method for high-resolution spatial sorting of hepatocytes based on zonated surface markers.
To reconstruct comprehensive spatial atlases of multiple zonated features, including mRNA, miRNA, and protein expression.
To investigate the relationship between mRNA and protein zonation and explore miRNA-mediated gene regulation in the liver lobule.

Main Methods:

Utilized zonated surface markers for high-resolution spatial sorting of hepatocytes.
Applied transcriptomics, miRNA array measurements, and mass spectrometry proteomics.
Integrated multi-omic data to reconstruct spatial atlases of liver cellular features.

Main Results:

Demonstrated largely overlapping spatial zonation patterns between proteins and their corresponding mRNAs, with HNF4α as a notable exception.
Identified specific zonation patterns for miRNAs, including miR-122.
Revealed inverse zonation between certain miRNAs and their target genes, suggesting miRNA-mediated regulation of protein levels via mRNA degradation, impacting Wnt signaling pathway components.

Conclusions:

The developed approach enables the reconstruction of detailed spatial atlases for multiple cellular features within the liver lobule.
Findings highlight the intricate spatial regulation of gene expression, miRNA activity, and protein levels in hepatocytes.
The study provides a framework for investigating tissue zonation in other complex organs.