Rat renal cell atlas and perturbation by losartan characterized with single-cell and spatial transcriptome information

To identify the local changes of the gene expression patterns by administration of losartan at single cell level, we performed both single cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) of the kidney from the rat treated with or without losartan. The sequencing library for scRNA-seq were prepared by Chromium Single Cell 3 Library Kit v2 (10x Genomics) and that for ST-seq were prepared by Visium Spatial Gene Expression Slide & Reagents Kit (10x Genomics). Following the integration analysis of scRNA-seq and ST-seq, we detected the spatially restricted changes of the gene expression patterns by administration of losartan in several cell types, such as macula densa cells or juxtaglomerular cells. We further analyze the ST-seq data in combination with the deconvolution tool, using scRNA-seq as a reference, and consequently observed spatial heterogeneity in the response to losartan among the glomeruli.

为在单细胞层面鉴定氯沙坦给药后基因表达模式的局部变化，我们对经氯沙坦处理与未处理的大鼠肾脏分别开展了单细胞RNA测序（single cell RNA sequencing, scRNA-seq）与空间转录组测序（spatial transcriptome sequencing, ST-seq）。单细胞RNA测序的测序文库采用Chromium Single Cell 3 Library Kit v2（10x Genomics）构建，空间转录组测序的测序文库则采用Visium Spatial Gene Expression Slide & Reagents Kit（10x Genomics）构建。在完成两类测序数据的整合分析后，我们在致密斑细胞（macula densa cells）、球旁细胞（juxtaglomerular cells）等多种细胞类型中，检测到氯沙坦给药引发的基因表达模式空间限制性变化。我们进一步以单细胞RNA测序数据作为参考数据集，结合反卷积分析工具对空间转录组测序数据开展联合分析，最终观察到不同肾小球对氯沙坦的应答存在空间异质性。