{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:20:16Z","timestamp":1790688016651,"version":"4.1.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01DK121037"],"award-info":[{"award-number":["R01DK121037"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"GOFARR Research Fund","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,22]]},"abstract":"<jats:p>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\u2013dependent 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.<\/jats:p>","DOI":"10.1172\/jci.insight.165515","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:26:26Z","timestamp":1712305586000},"source":"Crossref","is-referenced-by-count":22,"title":["The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0478-8520","authenticated-orcid":true,"given":"Geremy","family":"Clair","sequence":"first","affiliation":[{"name":"Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasmik","family":"Soloyan","sequence":"additional","affiliation":[{"name":"The GOFARR Laboratory, The Saban Research Institute, Division of Urology, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7837-0923","authenticated-orcid":true,"given":"Paolo","family":"Cravedi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-5326","authenticated-orcid":true,"given":"Andrea","family":"Angeletti","sequence":"additional","affiliation":[{"name":"Nephrology Dialysis and Renal Transplantation, IRCCS Istituto Giannina Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-2778","authenticated-orcid":true,"given":"Fadi","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laith","family":"Al-Rabadi","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger E.","family":"De Filippo","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA."},{"name":"Department of Urology, Keck School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-6822","authenticated-orcid":true,"given":"Stefano","family":"Da Sacco","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA."},{"name":"Department of Urology, Keck School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-5458","authenticated-orcid":true,"given":"Kevin V.","family":"Lemley","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sargis","family":"Sedrakyan","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA."},{"name":"Department of Urology, Keck School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Perin","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA."},{"name":"Department of Urology, Keck School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221810084"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00840.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09400913"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105412"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1683"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00037.2020"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-021-02133-8"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar2131"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908706116"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03634-9"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0623-0_21"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.08.005"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.4.326"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.12.018"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000517108"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05960616"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1106556"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11761116"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.17589.1"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202008-3303OC"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0975-3"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22331-9"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/biom13071139"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-019-0351-8"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0232-6"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018090912"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018020125"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01038-7"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0204-y"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.09.004"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00800.x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099083"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.06.015"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64802-X"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062095"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00288.x"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116923"},{"issue":"1-3","key":"B38","first-page":"17","article-title":"SRP-mediated protein targeting: structure and function revisited","volume":"1694","author":"Luirink","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.03.004"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012121217"},{"issue":"1\u20132","key":"B41","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s11010-008-9991-2","article-title":"Upregulation of the GRP-78 and GADD-153 and down regulation of Bcl-2 proteins in primary glomerular diseases: a possible involvement of the ER stress pathway in glomerulonephritis","volume":"324","author":"Markan","year":"2009","journal-title":"Mol Cell Biochem"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1159\/000210573"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.00903.x"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.389"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.5301\/jn.5000213"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2017.50.11.174"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1515\/bmc-2017-0007"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1271434"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200501000-00026"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009090991"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.12.028"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001577"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2003.09.010"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02629-7"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.2c00610"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr479"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00421"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369"},{"key":"B59","unstructured":"Monroe M. PNNL-Comp-Mass-Spec\/RomicsProcessor: Release 0.1.0. https:\/\/zenodo.org\/records\/3386527 Accessed February 19, 2024"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-9-r183"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5031"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/165515\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:40:38Z","timestamp":1779140438000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/165515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,2,15]]},"published-print":{"date-parts":[[2024,3,22]]}},"alternative-id":["10.1172\/jci.insight.165515"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.165515","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]},"article-number":"e165515"}}