Single-cell sequencing technologies have advanced our understanding of kidney biology and disease, but the loss of spatial information in these datasets hinders our interpretation of intercellular communication networks and regional gene expression patterns. New spatial transcriptomic sequencing platforms make it possible to measure the topography of gene expression at genome depth.

We optimized and validated a female bilateral ischemia-reperfusion injury model. Using the 10x Genomics Visium Spatial Gene Expression solution, we generated spatial maps of gene expression across the injury and repair time course, and applied two open-source computational tools, Giotto and SPOTlight, to increase resolution and measure cell-cell interaction dynamics.

An ischemia time of 34 minutes in a female murine model resulted in comparable injury to 22 minutes for males. We report a total of 16,856 unique genes mapped across our injury and repair time course. Giotto, a computational toolbox for spatial data analysis, enabled increased resolution mapping of genes and cell types. Using a seeded nonnegative matrix regression (SPOTlight) to deconvolute the dynamic landscape of cell-cell interactions, we found that injured proximal tubule cells were characterized by increasing macrophage and lymphocyte interactions even 6 weeks after injury, potentially reflecting the AKI to CKD transition.

In this transcriptomic atlas, we defined region-specific and injury-induced loss of differentiation markers and their re-expression during repair, as well as region-specific injury and repair transcriptional responses. Lastly, we created an interactive data visualization application for the scientific community to explore these results (http://humphreyslab.com/SingleCell/).

单细胞测序技术增进了我们对肾脏生物学和疾病的理解，但这些数据集中空间信息的丢失阻碍了我们对细胞间通讯网络和区域基因表达模式的解释。新的空间转录组测序平台使得测量基因组深度的基因表达拓扑成为可能。

我们优化并验证了女性双侧缺血再灌注损伤模型。使用 10 x Genomics Visium 空间基因表达解决方案，我们生成了整个损伤和修复时间过程中基因表达的空间图，并应用了两种开源计算工具 Giotto 和 SPOTlight 来提高分辨率并测量细胞间相互作用动态。

雌性小鼠模型中 34 分钟的缺血时间导致的损伤与雄性小鼠模型中 22 分钟的损伤相当。我们报告了总共 16,856 个独特基因，映射了我们的损伤和修复时间过程。Giotto 是一个用于空间数据分析的计算工具箱，可以提高基因和细胞类型映射的分辨率。使用种子非负矩阵回归 (SPOTlight) 对细胞间相互作用的动态景观进行解卷积，我们发现受伤的近曲小管细胞的特征是巨噬细胞和淋巴细胞相互作用增加，甚至在受伤后 6 周，这可能反映了 AKI 向 CKD 的转变。

在这个转录组图谱中，我们定义了区域特异性和损伤诱导的分化标记物的丢失及其在修复过程中的重新表达，以及区域特异性损伤和修复转录反应。最后，我们为科学界创建了一个交互式数据可视化应用程序来探索这些结果 (http://hummphreyslab.com/SingleCell/)。