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Updated: Sep 11, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Multimodal spatial transcriptomic characterization of mouse kidney injury and repair
Qiao Xuanyuan1, Haojia Wu1, Hemalatha Sundaramoorthi1
1Division of Nephrology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
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.
Insights
Researchers mapped kidney cells during injury and repair using spatial transcriptomics. They identified a fibro-inflammatory niche linked to chronic kidney disease progression, revealing key molecular drivers.
Area of Science:
- Renal biology
- Spatial transcriptomics
- Cellular and molecular pathology
Background:
- Acute kidney injury (AKI) can progress to chronic kidney disease (CKD).
- Understanding cellular and molecular changes during kidney repair is crucial for therapeutic development.
Purpose of the Study:
- To define cellular composition and molecular interactions in the kidney during injury and repair.
- To establish a multimodal spatial analytical framework for kidney research.
Main Methods:
- Analysis of over one million cells from 12 male mouse kidneys across six injury/repair stages.
- Utilized Xenium and whole transcriptome Visium spatial transcriptomics platforms.
- Multimodal spatial analysis to delineate cellular neighborhoods.
Main Results:
- Defined and validated 20 major kidney cell populations and distinct cellular neighborhoods.
- Identified a specific fibro-inflammatory niche containing failed-repair proximal tubule cells, fibroblasts, and immune cells.
- Revealed conserved neighborhood gene signatures in mouse and human, predicting Runx2, PDGF, and integrin beta-2 signaling pathways as key regulators.
Conclusions:
- The study provides deep insights into kidney injury and repair dynamics.
- A comprehensive multimodal analytical framework for spatial omics studies was established.
- Identified a specific fibro-inflammatory niche and its molecular drivers in kidney disease progression.
