Digital spatial profiling of collapsing glomerulopathy

Smith, Kelly D.; Prince, David K.; Henriksen, Kammi J.; Nicosia, Roberto F.; Alpers, Charles E.; Akilesh, Shreeram

doi:10.1016/j.kint.2022.01.033

Cited by 26 publications

(24 citation statements)

References 39 publications

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“…Spatial transcriptomic pro ling using a microdissection-based method, including GeoMX DSP, has particular strength the study of glomerular diseases, as the main focus of interest is usually on pathological changes in the glomerulus where most of the pathophysiological processes occur. 6,9,11 Although there are other types of RNA-seq-based spatial transcriptomic methods (e.g., Visium), current resolution is not su cient to capture the glomerulus-speci c transcriptome. 12 On the other hand, single-cell RNA-seq is another useful transcriptomic analysis method for investigating cell-speci c mRNA expression, 13 yet most single-cell human data include a relatively low portion of glomerulus cells with low feature variance.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Cho

Kang³

et al. 2023

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

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

Kim

Cho

Kang³

et al. 2023

Preprint

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“…By contrast, any fibrous transformation of glomerular structures and atrophy of kidney tubules or fibrosis within the interstitium indicate irreversible loss of kidney parenchyma. However, pathology lesion-based GN categories often do not dissect the diversity of underlying immunological disorders, which require different treatments 19 – 21 ; hence, treatment of lesion-based GN categories results in many ‘non-responders’ 22 .…”

Section: Clinical Presentation and Diagnosis Of Gnmentioning

confidence: 99%

“…High-risk APOL1 alleles also activate the NLRP3 inflammasome, with consequent release of IL-1β 49 that promotes the death of podocytes by pyroptosis 50 . In turn, APOL1 expression itself is upregulated by type I interferons and this further enhances podocyte loss 8 , in an autoactivation loop 21 , 50 . This may explain why Schistosoma infection-related GN progresses quickly to kidney failure in APOL1 carriers or in patients co-infected with HIV, HCV or HBV 8 .…”

Section: Infection-related Gnmentioning

confidence: 99%

Glomerulonephritis: immunopathogenesis and immunotherapy

et al. 2023

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‘Glomerulonephritis’ (GN) is a term used to describe a group of heterogeneous immune-mediated disorders characterized by inflammation of the filtration units of the kidney (the glomeruli). These disorders are currently classified largely on the basis of histopathological lesion patterns, but these patterns do not align well with their diverse pathological mechanisms and hence do not inform optimal therapy. Instead, we propose grouping GN disorders into five categories according to their immunopathogenesis: infection-related GN, autoimmune GN, alloimmune GN, autoinflammatory GN and monoclonal gammopathy-related GN. This categorization can inform the appropriate treatment; for example, infection control for infection-related GN, suppression of adaptive immunity for autoimmune GN and alloimmune GN, inhibition of single cytokines or complement factors for autoinflammatory GN arising from inborn errors in innate immunity, and plasma cell clone-directed or B cell clone-directed therapy for monoclonal gammopathies. Here we present the immunopathogenesis of GN and immunotherapies in use and in development and discuss how an immunopathogenesis-based GN classification can focus research, and improve patient management and teaching.

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“…These ROIs are then exposed to ultraviolet light to cleave the oligo probes that are collected and quantified on a custom nCounter analysis system or genomic sequencer. In this manner, ISH-based ST has allowed the visualization of tissue niches of interest in complex tissue sections such as brain [36][37][38] and liver 39 by MERFISH and kidney, 40,41 colon, 42 liver, 43 and lung 44 by GeoMx DSP. Based on the number of probes and size of tissue or ROI, both ISH-based ST techniques are simple, cost-effective, and high-throughput relative to ISS-based ST.…”

Section: Ish-based Stmentioning

confidence: 99%

The Utility of Spatial Transcriptomics for Solid Organ Transplantation

Raghubar

Matigian

et al. 2023

Transplantation

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Spatial transcriptomics (ST) measures and maps transcripts within intact tissue sections, allowing the visualization of gene activity within the spatial organization of complex biological systems. This review outlines advances in genomic sequencing technologies focusing on in situ sequencing–based ST, including applications in transplant and relevant nontransplant settings. We describe the experimental and analytical pipelines that underpin the current generation of spatial technologies. This context is important for understanding the potential role ST may play in expanding our knowledge, including in organ transplantation, and the important caveats/limitations when interpreting the vast data output generated by such methodological platforms.

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Digital spatial profiling of collapsing glomerulopathy

Cited by 26 publications

References 39 publications

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

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

Glomerulonephritis: immunopathogenesis and immunotherapy

The Utility of Spatial Transcriptomics for Solid Organ Transplantation

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