Identification of conserved gene expression changes across common glomerular diseases by spatial transcriptomics

초록

Background Glomerular diseases encompass a group of kidney diseases that may share common gene expression pathways. Here, we analyzed glomerular-specifc gene expression profles across various glomerular diseases. Methods We performed spatial transcriptomic profling using formalin-fxed parafn-embedded kidney biopsy specimens of controls and patients with fve types of glomerular diseases using the GeoMx Digital Spatial Profler. Disease-representative glomerular regions of interest (ROIs) were confgured, probed with oligonucleotide barcodes linked with target complimentary sequence. The UV-cleaved barcodes were amplifed to generate libraries and subsequently sequenced. Common diferentially expressed genes across glomerular diseases were identifed and Gene Ontology annotation was performed using the ToppGene suite. Results The mean age of patients with glomerular diseases and kidney donors was 49.5±12.2 and 49.5±9.8 years, respectively. A total of 35 diferentially expressed genes were consistently downregulated in glomeruli across the disease compared to the control, while none of the diferentially expressed genes were consistently upregulated. Twelve of 35 downregulated diferentially expressed genes, including the two hub genes JUN and FOS, were annotated with molecular function Gene Ontology terms related to DNA-binding transcription factor activity. The annotated biological process Gene Ontology terms included response to lipid-related (17/35 diferentially expressed genes), response to steroid hormone (12/35 diferentially expressed genes), or cell cycle regulation (10/35 diferentially expressed genes). Xenium and immunofuorescence staining confrmed the reduced expression of JUN, ZFP36, and KLF9 in intraglomerular cells of glomerular diseases.

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