The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease.
| Title: | The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease. |
|---|---|
| Authors: | Clair G; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.; Soloyan H; The GOFARR Laboratory, The Saban Research Institute, Division of Urology, Children's Hospital Los Angeles, Los Angeles, California, USA.; Cravedi P; Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Angeletti A; Nephrology Dialysis and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genova, Italy.; Salem F; Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.; Al-Rabadi L; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, USA.; De Filippo RE; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.; Department of Urology, Keck School of Medicine, and.; Da Sacco S; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.; Department of Urology, Keck School of Medicine, and.; Lemley KV; Division of Nephrology, Department of Pediatrics, University of Southern California, Los Angeles, California, USA.; Sedrakyan S; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.; Department of Urology, Keck School of Medicine, and.; Perin L; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.; Department of Urology, Keck School of Medicine, and. |
| Source: | JCI insight [JCI Insight] 2024 Mar 22; Vol. 9 (6). Date of Electronic Publication: 2024 Mar 22. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| MeSH Terms: | Glomerulosclerosis, Focal Segmental*/pathology ; Nephritis, Hereditary*/pathology ; Renal Insufficiency, Chronic*/metabolism; Kidney Glomerulus/pathology ; Humans ; Transcriptome |
| Abstract: | 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. |
| References: | Bioinformatics. 2011 Oct 15;27(20):2866-72. (PMID: 21852304); Am J Kidney Dis. 2004 Jan;43(1):19-27. (PMID: 14712423); Am J Pathol. 2000 Nov;157(5):1649-59. (PMID: 11073824); Kidney Int. 2003 Nov;64(5):1715-21. (PMID: 14531804); Kidney Int. 2010 Feb;77(3):187-93. (PMID: 19812538); Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1461-9. (PMID: 24875196); J Am Soc Nephrol. 2019 Jan;30(1):23-32. (PMID: 30510133); Matrix Biol. 2017 Jan;57-58:45-54. (PMID: 27576055); Int J Mol Sci. 2020 Mar 18;21(6):. (PMID: 32197499); Proc Natl Acad Sci U S A. 2019 Sep 24;116(39):19619-19625. (PMID: 31506348); Nat Metab. 2020 May;2(5):461-474. (PMID: 32694662); F1000Res. 2019 May 24;8:. (PMID: 31168358); Nephron Exp Nephrol. 2009;112(1):e1-9. (PMID: 19342868); Sci Data. 2020 Jan 2;7(1):4. (PMID: 31896769); Kidney Int. 2006 Aug;70(3):529-35. (PMID: 16775597); Kidney Int Rep. 2017 Mar 27;2(4):739-748. (PMID: 29142990); Kidney Int. 2022 Jan;101(1):131-136. (PMID: 34555393); Nat Commun. 2021 Apr 9;12(1):2141. (PMID: 33837218); Mol Cell Biochem. 2009 Apr;324(1-2):131-8. (PMID: 19107326); J Hypertens. 2005 Jan;23(1):153-64. (PMID: 15643138); N Engl J Med. 2011 Dec 22;365(25):2398-411. (PMID: 22187987); Genome Biol. 2016 May 23;17(1):106. (PMID: 27215581); Int J Mol Sci. 2021 Sep 18;22(18):. (PMID: 34576247); Nature. 2021 Aug;596(7871):211-220. (PMID: 34381231); Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. (PMID: 28550082); Methods Mol Biol. 2020;2148:331-345. (PMID: 32394392); Genome Biol. 2022 Mar 7;23(1):73. (PMID: 35255944); Traffic. 2009 Jun;10(6):673-90. (PMID: 19302420); Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198. (PMID: 31066453); Biochim Biophys Acta. 2004 Nov 11;1694(1-3):17-35. (PMID: 15546655); Biomolecules. 2023 Jul 17;13(7):. (PMID: 37509175); Kidney Int. 2018 Jun;93(6):1298-1307. (PMID: 29678354); Annu Rev Physiol. 2016;78:437-61. (PMID: 26863327); J Mol Med (Berl). 2021 Dec;99(12):1727-1740. (PMID: 34528115); Science. 2018 May 18;360(6390):758-763. (PMID: 29622724); Biomol Concepts. 2017 May 24;8(2):93-104. (PMID: 28574376); Front Genet. 2019 May 03;10:421. (PMID: 31130993); J Am Soc Nephrol. 2010 Jul;21(7):1145-56. (PMID: 20522532); J Proteome Res. 2023 Feb 3;22(2):570-576. (PMID: 36622218); J Am Soc Nephrol. 2014 Feb;25(2):260-75. (PMID: 24262798); J Nephrol. 2013 Mar-Apr;26(2):266-72. (PMID: 23023721); Science. 2019 Sep 27;365(6460):1461-1466. (PMID: 31604275); Am J Pathol. 2013 Oct;183(4):1269-1280. (PMID: 23911822); Nat Rev Nephrol. 2020 Apr;16(4):238-250. (PMID: 31853010); J Med Genet. 1997 Apr;34(4):326-30. (PMID: 9138159); Diabetes. 2006 Oct;55(10):2747-56. (PMID: 17003339); J Am Soc Nephrol. 2001 Jul;12(7):1434-1447. (PMID: 11423572); Nat Methods. 2021 Jan;18(1):15-18. (PMID: 33408402); Kidney Dis (Basel). 2021 Sep;7(5):350-358. (PMID: 34604342); Am J Respir Crit Care Med. 2022 Jan 15;205(2):208-218. (PMID: 34752721); Kidney Int. 2003 Mar;63(3):809-25. (PMID: 12631062); Kidney Int. 2003 Mar;63(3):826-34. (PMID: 12631063); Genome Biol. 2007;8(9):R183. (PMID: 17784955); J Am Soc Nephrol. 2018 Aug;29(8):2069-2080. (PMID: 29980650); Am J Physiol Renal Physiol. 2020 Nov 1;319(5):F809-F821. (PMID: 32954852); Kidney Int. 2018 May;93(5):1045-1051. (PMID: 29551517); PLoS One. 2014 Jun 10;9(6):e99083. (PMID: 24915008); Clin J Am Soc Nephrol. 2017 Mar 7;12(3):502-517. (PMID: 28242845); Life Sci. 2019 Dec 1;238:116923. (PMID: 31610191); BMB Rep. 2017 Nov;50(11):572-577. (PMID: 29065969) |
| Grant Information: | R01 DK121037 United States DK NIDDK NIH HHS; U54 DK083912 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: Chronic kidney disease; Nephrology |
| Entry Date(s): | Date Created: 20240322 Date Completed: 20240325 Latest Revision: 20250924 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11063942 |
| DOI: | 10.1172/jci.insight.165515 |
| PMID: | 38516889 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't