Identification of Conserved Gene Expression Changes Across Common Glomerular Diseases by Spatial Transcriptomics

Abstract Background: Glomerular diseases encompass a group of kidney diseases that may share common gene expression pathways. We aimed to analyze glomerular-specific gene expression profiles across various glomerular diseases. Methods: We performed spatial transcriptomic profiling using formalin-fixed paraffin-embedded kidney biopsy specimens of controls and patients with five types of glomerular diseases using the GeoMx Digital Spatial Profiler. We identified common differentially expressed genes (DEGs) across glomerular diseases and performed Gene Ontology (GO) annotation by using the ToppGene suite. Results: A total of 35 DEGs were consistently downregulated in glomeruli across the disease compared to the control, while none of the DEGs were consistently upregulated. Twelve of 35 downregulated DEGs, including the two hub genes FOS and JUN, were annotated with molecular function GO terms related to DNA-binding transcription factor activity. Other notable DEGs consistently downregulated and annotated in the pathway analysis included NR4A3, KLF9, EGR1, and ATF3. The annotated biological process GO terms included response to lipid-related (17/35 DEGs), response to steroid hormone (12/35 DEGs), or cell cycle regulation (10/35 DEGs). Conclusions: Identifying common DEGs by spatial transcriptomic analysis provides insights into the underlying molecular mechanisms of glomerular diseases and may lead to novel assessment or therapeutic strategies.