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Using translating ribosome affinity purification RNASeq on mouse kidneys with polycystin-1 and cilia inactivation before cyst formation, we identify the differential \u2018CDCA pattern\u2019 translatome specifically dysregulated in kidney tubule cells destined to form cysts. From this,\n                    <jats:italic>Glis2<\/jats:italic>\n                    emerges as a candidate functional effector of polycystin signaling and CDCA. In vitro changes in\n                    <jats:italic>Glis2<\/jats:italic>\n                    expression mirror the polycystin- and cilia-dependent changes observed in kidney tissue, validating\n                    <jats:italic>Glis2<\/jats:italic>\n                    as a cell culture-based indicator of polycystin function related to cyst formation. Inactivation of\n                    <jats:italic>Glis2<\/jats:italic>\n                    suppresses polycystic kidney disease in mouse models of ADPKD, and pharmacological targeting of\n                    <jats:italic>Glis2<\/jats:italic>\n                    with antisense oligonucleotides slows disease progression.\n                    <jats:italic>Glis2<\/jats:italic>\n                    transcript and protein is a functional target of CDCA and a potential therapeutic target for treating ADPKD.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-48025-6","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T12:02:00Z","timestamp":1714564920000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0451-3077","authenticated-orcid":false,"given":"Chao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1335-5380","authenticated-orcid":false,"given":"Steven Lim Cho","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"3rd","given":"Thomas A.","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1943-017X","authenticated-orcid":false,"given":"Ke","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1726-0899","authenticated-orcid":false,"given":"Ming Shen","family":"Tham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-7275","authenticated-orcid":false,"given":"Yiqiang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-3866","authenticated-orcid":false,"given":"Zemeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6841-4192","authenticated-orcid":false,"given":"Felix","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton M.","family":"Jetten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-9607","authenticated-orcid":false,"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-6293","authenticated-orcid":false,"given":"Monkol","family":"Lek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-4629","authenticated-orcid":false,"given":"Stefan","family":"Somlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"48025_CR1","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S0140-6736(18)32782-X","volume":"393","author":"E Cornec-Le Gall","year":"2019","unstructured":"Cornec-Le Gall, E., Alam, A. & Perrone, R. 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