Spatially resolved transcriptomic analysis of acute kidney injury in a female murine model

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 males across the time course of injury and repair. We report increased resolution of cell and gene expression with Giotto, a computational toolbox for spatial data analysis. Using a seeded non-negative matrix regression (SPOTlight) to deconvolute the dynamic landscape of cell-cell interactions, we find that injured proximal tubule cells are characterized by increasing macrophage and lymphocyte interactions even at 6 weeks after injury, consistent with a pro-inflammatory role for this cell state. 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 a data visualization web application for the scientific community to explore these results (http://humphreyslab.com/SingleCell/).