Paired-cell sequencing enables spatial gene expression mapping of liver endothelial cells

Nature Biotechnology
Keren Bahar HalpernShalev Itzkovitz

Abstract

Spatially resolved single-cell RNA sequencing (scRNAseq) is a powerful approach for inferring connections between a cell's identity and its position in a tissue. We recently combined scRNAseq with spatially mapped landmark genes to infer the expression zonation of hepatocytes. However, determining zonation of small cells with low mRNA content, or without highly expressed landmark genes, remains challenging. Here we used paired-cell sequencing, in which mRNA from pairs of attached mouse cells were sequenced and gene expression from one cell type was used to infer the pairs' tissue coordinates. We applied this method to pairs of hepatocytes and liver endothelial cells (LECs). Using the spatial information from hepatocytes, we reconstructed LEC zonation and extracted a landmark gene panel that we used to spatially map LEC scRNAseq data. Our approach revealed the expression of both Wnt ligands and the Dkk3 Wnt antagonist in distinct pericentral LEC sub-populations. This approach can be used to reconstruct spatial expression maps of non-parenchymal cells in other tissues.

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Methods Mentioned

BETA
RNA-Seq
scRNAseq
FACS
smFISH
pcRNAseq
RNAseq
flow cytometry
in
PCR
PCA

Software Mentioned

Cytoscape
HISAT
R
Matlab
IDEAS
PcRNAseq
smFISH
Seurat

Related Concepts

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