The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease
Here, we used Digital Spatial Profiling (DSP) to describe the glomerular transcriptomic signatures that may characterize the complex molecular mechanisms underlying progressive kidney disease in Alport syndrome, focal segmental glomerulosclerosis, and membranous nephropathy. Our results revealed significant transcriptional heterogeneity among diseased glomeruli, and this analysis showed that histologically similar glomeruli manifested different transcriptional profiles. Using glomerular pathology scores to establish an axis of progression, we identified molecular pathways that progressively decreased with increasing pathology scores, including Signal Recognition Particle-dependent co-translational protein targeting to membrane and selenocysteine synthesis pathways. We also identified a distinct signature of upregulated and downregulated genes common to all the diseases investigated when compared to non-diseased tissue from nephrectomies. These analyses using DSP at the single glomerulus level could help to gain insight into the pathophysiology of kidney disease Overall design: Serially sectioned formalin fixed and paraffin embedded kidney biopsies from healthy control pateints (n=3) and patients affected with Alport syndrome (n=3), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=2) were processed for digital spatial profiling to explore compartment-specific transcriptional programs of the selected 75 glomeruar and 31 tubular regions.