{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:45:12Z","timestamp":1786466712673,"version":"build-2736575974"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["K08 DK131258"],"award-info":[{"award-number":["K08 DK131258"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007172","name":"CCHMC","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007172","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:p>\n                    While Wilms tumors commonly arise from renal precursor cells and maintain features of the developing kidney, recent studies have demonstrated substantial genetic, histologic, and molecular heterogeneity. To further investigate tumor variability as well as unifying features in tumor biology, we performed single-nucleus RNA sequencing (snRNA-seq) on treatment-naive, favorable-histology Wilms tumors utilizing a reference atlas established from tumor-adjacent kidney samples and fetal kidney. Transcriptional profiles of blastemal, stromal, and epithelial components were correlated with tumor histology and demonstrated developmental-lineage plasticity, with\n                    <jats:italic>PAX2<\/jats:italic>\n                    and\n                    <jats:italic>PAX8<\/jats:italic>\n                    expression normally restricted to the nephron lineage of the fetal kidney found to be expressed in tumor stroma, as well as the stromal marker\n                    <jats:italic>POSTN<\/jats:italic>\n                    identified in tumor blastema. Further analyses of the blastema show shared transcriptional features with the differentiation trajectory of \u201cuninduced\u201d to \u201cearly differentiating\u201d fetal nephron progenitor cells as well as aberrant expression of stromal signatures. A number of pathways from fetal nephron progenitors were maintained in the blastema, including regulation of stem cell maintenance and axonogenesis, whereas other pathways appear enriched in specific tumor samples, demonstrating the ability of snRNA-seq to identify both unifying transcriptional signatures and uncover distinct molecular targets in signaling pathways and\/or biological drivers of Wilms tumorigenesis.\n                  <\/jats:p>\n                  <jats:p\/>\n                  <jats:p>Wilms tumors commonly arise from and maintain features of the developing kidney, this embryonal tumor has been shown to exhibit surprisingly heterogeneous genetic, histological, and molecular landscapes.<\/jats:p>","DOI":"10.1172\/jci.insight.188078","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:01:13Z","timestamp":1781020873000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-nucleus RNA sequencing reveals transcriptional heterogeneity in the blastema of favorable-histology Wilms tumor"],"prefix":"10.1172","volume":"11","author":[{"given":"Mike","family":"Adam","sequence":"first","affiliation":[{"name":"Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri A.","family":"Drake","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Pode-Shakked","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, Dana Dwek Children\u2019s Hospital, Tel Aviv Sourasky University Medical Center (Ichilov), Tel Aviv, Israel."},{"name":"Grey Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"VandenHeuvel","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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