Spatial transcriptomics reveals injured cells, signature genes, and communication patterns in the cyst microenvironment of Polycystic Kidney Disease
Evidence indicates that changes in the cyst microenvironment in Polycystic Kidney Disease (PKD) may drive progressive cyst formation. Bulk- and single-cell RNA sequencing have advanced our understanding of altered signaling, however, the lack of spatial information has limited our insights into local gene expression and cellular communication near cysts. We used wild-type and Pkd1-deficient mouse kidneys to generate 10x Genomics Visium Spatial Gene Expression datasets. Utilizing our our single-cell mouse kidney atlas for spot deconvolution, we enhanced the resolution and estimated enriched cell types. We analyzed spatial gene expression patterns and used a cyst-centered analysis to identify a cyst-associated gene signature. Cell communication near cysts was investigated, identifying key ligand-receptors. Expression of key ligandsAntibody staining was validated inperformed on human tissues. We found an enrichment of fibroblasts, injury-repair-related cell types, and various immune cells in PKD. Failed-repair proximal tubule cells were exclusively found in PKD, primarily condensed in immune cell-dense regions near cysts. These cells collectively contributed to the altered gene expression profile in PKD, and cyst-associated signature genes related to inflammatory processes.