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Abstract: FR-PO680

Spatially Resolved Transcriptomic Profiling for Glomerular and Tubulointerstitial Gene Expression in C3 Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Koh, Jung Hun, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Park, Sehoon, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Cho, Jeongmin, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Yaerim, Keimyung University Dongsan Medical Center, Daegu, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background

C3 glomerulonephritis (C3GN) is a rare but clinically significant primary glomerulopathy. However, little is known about its transcriptomic profile. We aimed to investigate the substructure-specific gene expression profile of C3GN using the recently introduced spatial transcriptomics technology.

Methods

We performed spatial transcriptomic profiling using GeoMx Digital Spatial Profiler with formalin-fixed paraffin-embedded kidney biopsy specimens of three C3GN cases and eight donor kidney controls. Profiles from other glomerular diseases, including focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease, were included as disease controls. Gene expression levels between C3GN and the controls were compared by DESeq2 method, and differentially expressed genes (DEGs) were identified with a false discovery rate threshold of 0.05. We performed gene ontology (GO) annotation by the ToppGene Suite and mapped interaction networks among the DEGs using the STRING database.

Results

We identified 229 and 157 highly expressed DEGs in the glomeruli of C3GN compared to those of donor and disease controls, respectively, with consistently highest fold changes seen in POSTN, COL1A2, IFI44L, and TAGLN. Protease binding, structural molecule activity, and extracellular matrix constituent were the top enriched GO terms in the glomeruli of C3GNs, with consistent features seen in the network analysis. In contrast, no significant GO enrichment was found among the 563 and 347 lowly expressed DEGs in the glomeruli of C3GN compared to donor and disease controls. The tubular transcriptome profiles of C3GN were similar to those of the controls.

Conclusion

This is the first report of kidney substructure-specific transcriptomic profile of C3GN to date. Significant disease-specific transcriptomic alterations occur in the glomerulus of C3GN, providing potential insights into the pathophysiology.

STRING network analysis of highly expressed DEGs in C3GN glomerulus compared to (A) donor and (B) disease controls.

Funding

  • Government Support – Non-U.S.