Spatially resolved transcriptomic profiling for glomerular and tubulointerstitial gene expression in C3...

Area of Science:

• Nephrology
• Molecular Biology
• Genomics

Background:

• Complement 3 (C3) glomerulopathy (C3G) is a rare but significant kidney disease.
• The transcriptomic profile of C3G remains largely unknown.
• Spatial transcriptomics offers a novel approach to investigate C3G at a substructure level.

Purpose of the Study:

• To investigate the substructure-specific gene expression profile of C3G.
• To identify differentially expressed genes (DEGs) in C3G kidney tissue.
• To explore the potential role of identified DEGs in C3G pathophysiology.

Main Methods:

• Spatial transcriptomic profiling using GeoMx Digital Spatial Profiler on kidney biopsy specimens.
• Comparison of three C3G cases with seven donor controls and 41 other glomerulonephritis cases.
• In vitro validation of upregulated DEGs in human glomerular endothelial cells co-cultured with complement-stimulated macrophages.

Main Results:

• Identified 229 and 157 highly expressed DEGs in C3G glomeruli compared to controls.
• Top enriched Gene Ontology terms included protease binding and extracellular matrix (ECM) structural constituent.
• Genes related to ECM and interferon activity were significantly upregulated, with potential interactions between complement C3 and ECM.

Conclusions:

• C3G exhibits significant, disease-specific transcriptomic alterations.
• Upregulation of ECM-related genes provides potential insights into C3G pathophysiology.
• Further research into these transcriptomic changes may reveal novel therapeutic targets.