Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Nat Biotechnol. 2018 Nov;36(10):962-970. doi: 10.1038/nbt.4231. Epub 2018 Sep 17.
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.
空间分辨单细胞 RNA 测序 (scRNAseq) 是一种推断细胞身份与其在组织中位置之间关系的强大方法。我们最近将 scRNAseq 与空间映射的标志性基因结合起来,以推断肝细胞的表达分区。然而,确定具有低 mRNA 含量的小细胞或没有高度表达的标志性基因的分区仍然具有挑战性。在这里,我们使用配对细胞测序,对附着的小鼠细胞对中的 mRNA 进行测序,并使用一种细胞类型的基因表达来推断细胞对的组织坐标。我们将这种方法应用于肝细胞和肝内皮细胞 (LEC) 的配对。利用来自肝细胞的空间信息,我们重建了 LEC 的分区,并提取了一个标志性基因面板,我们用它来对 LEC scRNAseq 数据进行空间映射。我们的方法揭示了 Wnt 配体和 Dkk3 Wnt 拮抗剂在不同的中央周向 LEC 亚群中的表达。这种方法可用于重建其他组织中非实质细胞的空间表达图谱。
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