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Using PT-specific genetic deletion in mice, we found that loss of\n                  <jats:italic>Hnf1b<\/jats:italic>\n                  in differentiated PT cells causes cyst formation and early postnatal lethality. PT-specific transcriptomic analysis revealed downregulation of PT-specific gene programs, including\n                  <jats:italic>Hnf4a<\/jats:italic>\n                  and PT-enriched transport and metabolic genes. Strikingly,\n                  <jats:italic>Hnf1b<\/jats:italic>\n                  -deficient PT cells ectopically activated podocyte-specific genes, including\n                  <jats:italic>Wt1<\/jats:italic>\n                  and\n                  <jats:italic>Nphs1<\/jats:italic>\n                  , demonstrating that PT cells retain the capacity to engage alternative nephron segment programs when identity-stabilizing mechanisms are disrupted. In addition, loss of\n                  <jats:italic>Hnf1b<\/jats:italic>\n                  disrupted epithelial integrity, as evidenced by reduced epithelial adhesion gene expression and induction of mesenchymal markers. Wnt\/\u03b2-catenin signaling was also aberrantly activated, suggesting broader dysregulation of epithelial homeostasis. These findings establish HNF1B as a critical post-specification regulator of PT identity that sustains PT-specific transcriptional programs and actively suppresses alternative segmental identity programs.\n                <\/jats:p>","DOI":"10.64898\/2026.08.12.744527","type":"posted-content","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:05:16Z","timestamp":1786662316000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of\n                  <i>Hnf1b<\/i>\n                  in differentiated proximal tubule cells uncovers nephron segment plasticity"],"prefix":"10.64898","author":[{"given":"Zeinab","family":"Dehghani-Ghobadi","sequence":"first","affiliation":[{"name":"Feinberg Cardiovascular & Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunah","family":"Chung","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular & Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Haghighitalab","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular & Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Sayed","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueh-Chiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Woong","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4190-4386","authenticated-orcid":false,"given":"Joo-Seop","family":"Park","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular & Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"},{"name":"Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081703401359000_2026.08.12.744527v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2015.10.010"},{"key":"2026081703401359000_2026.08.12.744527v1.2","doi-asserted-by":"crossref","unstructured":"Schnell J , Achieng M , and Lindstr\u00f6m NO . 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