{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:16:16Z","timestamp":1793142976403,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2019,1]]},"abstract":"\n Background<\/jats:title>\n Notch signaling is required during kidney development for nephron formation and principal cell fate selection within the collecting ducts. Whether Notch signaling is required in the adult kidney to maintain epithelial diversity, or whether its loss can trigger principal cell transdifferentiation (which could explain acquired diabetes insipidus in patients receiving lithium) is unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To investigate whether loss of Notch signaling can trigger principal cells to lose their identity, we genetically inactivated\n Notch1<\/jats:italic>\n and\n Notch2<\/jats:italic>\n , inactivated the Notch signaling target\n Hes1<\/jats:italic>\n , or induced expression of a Notch signaling inhibitor in all of the nephron segments and collecting ducts in mice after kidney development. We examined renal function and cell type composition of control littermates and mice with conditional Notch signaling inactivation in adult renal epithelia. In addition, we traced the fate of genetically labeled adult kidney collecting duct principal cells after\n Hes1<\/jats:italic>\n inactivation or lithium treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Notch signaling was required for maintenance of Aqp2-expressing cells in distal nephron and collecting duct segments in adult kidneys. Fate tracing revealed mature principal cells in the inner stripe of the outer medulla converted to intercalated cells after genetic inactivation of\n Hes1<\/jats:italic>\n and, to a lesser extent, lithium treatment.\n Hes1<\/jats:italic>\n ensured repression of\n Foxi1<\/jats:italic>\n to prevent the intercalated cell program from turning on in mature Aqp2\n +<\/jats:sup>\n cell types.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Notch signaling\n via<\/jats:italic>\n Hes1<\/jats:italic>\n regulates maintenance of mature renal epithelial cell states. Loss of Notch signaling or use of lithium can trigger transdifferentiation of mature principal cells to intercalated cells in adult kidneys.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2018040440","type":"journal-article","created":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T19:15:11Z","timestamp":1543950911000},"page":"110-126","source":"Crossref","is-referenced-by-count":56,"title":["Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis"],"prefix":"10.1681","volume":"30","author":[{"given":"Malini","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Pediatrics and Rare Diseases Group and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"deRiso","sequence":"additional","affiliation":[{"name":"Pediatrics and Rare Diseases Group and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Otterpohl","sequence":"additional","affiliation":[{"name":"Enabling Technologies Group, Sanford Research, Sioux Falls, South Dakota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishara","family":"Ratnayake","sequence":"additional","affiliation":[{"name":"Department of Nanoscience and Nanoengineering, South Dakota School of Mines and Technology, Rapid City, South Dakota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Kota","sequence":"additional","affiliation":[{"name":"Department of Nanoscience and Nanoengineering, South Dakota School of Mines and Technology, Rapid City, South Dakota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Ahrenkiel","sequence":"additional","affiliation":[{"name":"Department of Nanoscience and Nanoengineering, South Dakota School of Mines and Technology, Rapid City, South Dakota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra","family":"Chandrasekar","sequence":"additional","affiliation":[{"name":"Enabling Technologies Group, Sanford Research, Sioux Falls, South Dakota;"},{"name":"Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kameswaran","family":"Surendran","sequence":"additional","affiliation":[{"name":"Pediatrics and Rare Diseases Group and"},{"name":"Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,12,4]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1242\/dev.092551","article-title":"Induced pluripotent stem cells in medicine and 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