Integration of spatial and single-nucleus transcriptomics to map gene expression in the developing mouse kidney.
Christopher P Chaney, Alexandria N Fusco, Elyse D Grilli, Jane N Warshaw, Peter M Luo, Ondine Cleaver, Denise K Marciano, Thomas J Carroll
Abstract
Open AccessThe kidney is a complex organ requiring tightly coordinated interactions between epithelial, endothelial and mesenchymal cells during development. Congenital kidney defects can result in kidney disease and renal failure, highlighting the importance of understanding kidney formation mechanisms. Advances in RNA sequencing have revealed remarkable cellular heterogeneity, especially in the kidney stroma, although relationships between stromal, epithelial and endothelial cells remain unclear. This study presents a comprehensive gene expression atlas of embryonic and postnatal kidneys, integrating single-nucleus and in situ RNA sequencing data. We developed the Kidney Spatial Transcriptome Analysis Tool (KSTAT), enabling researchers to identify cell locations, predict cell-cell communication and map gene pathway activity. Using KSTAT, we were able to uncover significant heterogeneity among embryonic kidney pericytes, providing an important resource for hypothesis generation and advancing knowledge of kidney development and disease.