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 with progressively decreased expression in response to increasing pathology scores, including signal recognition particle-dependent cotranslational 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 with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
JCI insight - 9(2024), 6 vom: 22. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Clair, Geremy [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.165515 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370064682 |
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| 520 | |a 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 with progressively decreased expression in response to increasing pathology scores, including signal recognition particle-dependent cotranslational 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 with nondiseased tissue from nephrectomies. These analyses using DSP at the single-glomerulus level could help to increase insight into the pathophysiology of kidney disease and possibly the identification of biomarkers of disease progression in glomerulopathies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic kidney disease | |
| 650 | 4 | |a Nephrology | |
| 700 | 1 | |a Soloyan, Hasmik |e verfasserin |4 aut | |
| 700 | 1 | |a Cravedi, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Angeletti, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Salem, Fadi |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Rabadi, Laith |e verfasserin |4 aut | |
| 700 | 1 | |a De Filippo, Roger E |e verfasserin |4 aut | |
| 700 | 1 | |a Da Sacco, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Lemley, Kevin V |e verfasserin |4 aut | |
| 700 | 1 | |a Sedrakyan, Sargis |e verfasserin |4 aut | |
| 700 | 1 | |a Perin, Laura |e verfasserin |4 aut | |
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