{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:13:03Z","timestamp":1792447983983,"version":"4.5.0"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370717"],"award-info":[{"award-number":["82370717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LR26H050001"],"award-info":[{"award-number":["LR26H050001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ23H050001"],"award-info":[{"award-number":["LZ23H050001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,24]]},"abstract":"<jats:p>\n                    Podocytes (PODs) play a critical role in maintaining glomerular filtration function, and their injury is a key driver of progressive podocytopathies (PCPs). Despite their clinical importance, the molecular and spatial mechanisms underlying POD injury remain poorly understood. We generated a single-nucleus RNA sequencing (snRNA-seq) and high-resolution spatial transcriptomic (ST) dataset from kidney tissues of patients with five major PCP subtypes. Our analysis revealed distinct molecular signatures among PCP subtypes, injury-related cytoskeletal alterations, and POD-centered microenvironmental features associated with clinical outcomes. Through integrative analysis, we found\n                    <jats:italic toggle=\"yes\">PDE4DIP<\/jats:italic>\n                    as a previously unrecognized regulator of the POD cytoskeleton. Functional experiments through in vitro and in vivo gene editing demonstrated that PDE4DIP maintains cytoskeletal integrity by scaffolding with AKAP9 and activating RAS-ERK and AKT signaling. Its expression correlated with renal function and prognosis. This study provides the comprehensive snRNA-seq and high-resolution ST atlas of PCPs, offering a valuable resource for understanding POD injury and identifying potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw9707","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:58:33Z","timestamp":1784915913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell and high-resolution spatial profiling of podocytopathies reveals core mechanisms of podocyte injury"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-3389","authenticated-orcid":true,"given":"Jianbo","family":"Qing","sequence":"first","affiliation":[{"name":"Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, 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