A cross model spatial and single-cell atlas reveals the conserved involvement of osteopontin in polycystic kidney disease

To elucidate the cellular and molecular consequences of these mutations, we constructed an integrated single-cell and spatial transcriptomics atlas across mouse models of PKD, mapping changes in cell type composition, gene expression, and intercellular signaling networks.

Single-cell and spatial transcriptomics revealed elevated Spp1 (osteopontin) expression enhanced signaling interactions with macrophages and fibroblasts in cystic niches. Whereas deletion of Spp1 increased cyst severity in the Ift88 model, it reduced PKD severity in the orthologous Pkd1RC/RC model, concurrent with model-specific differences in Spp1 cell type expression and communication partners. We also found increased SPP1 expression and signaling in single-cell RNA sequencing data from autosomal dominant PKD (ADPKD) patients, highlighting cross-species conservation.