Multimodal spatial transcriptomic characterization of mouse kidney injury and repair
Qiao Xuanyuan, Hao Wu, Hemalatha Sundaramoorthi, Pierre Isnard, Changfeng Chen, Waleed Rahmani, Benjamin D. Humphreys
Abstract
The transition from acute kidney injury to chronic kidney disease is characterized by significant changes in the cellular composition and molecular interactions within the kidney. Utilizing high-resolution Xenium and whole transcriptome Visium spatial transcriptomics platforms, we analyze over a million cells on 12 male mouse kidneys across six stages of renal injury and repair. We define and validate 20 major kidney cell populations and delineate distinct cellular neighborhoods through this multimodal spatial analysis. We further reveal a specific fibro-inflammatory niche enriched in failed-repair proximal tubule cells, fibroblasts, and immune cells, with conserved neighborhood gene signatures across mouse and human. Within this niche, we predict Runx2 as a key upstream regulator, along with platelet-derived growth factor and integrin beta-2 signaling pathways shaping the fibrogenic microenvironment. Altogether, our study provides deep insights into the cellular and molecular dynamics during kidney injury and repair and establishes a comprehensive multimodal analytical framework applicable to other spatial omics studies. Kidney injury progression involves complex changes in cellular composition and spatial organization. Here, the authors use multimodal spatial transcriptomics to reveal fibro-inflammatory niche with Runx2 and integrin beta-2 driving fibrotic remodeling.