{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:00:27Z","timestamp":1785168027798,"version":"3.55.0"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gallbladder cancer (GBC) is a highly lethal malignancy with limited experimental models to study disease biology or evaluate therapeutic responses. Although canonical Wnt activation is commonly used for patient\u2010derived organoid (PDO) development and expansion, gallbladder PDOs have also been generated under Wnt\u2010inhibitory conditions. No comparative assessments have determined how Wnt pathway modulation influences gallbladder PDO development, phenotype, or drug response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study systematically compared the impact of canonical Wnt activation (WNT\n                      <jats:sup>Act<\/jats:sup>\n                      medium containing CHIR99021) versus inhibition (WNT\n                      <jats:sup>Inh<\/jats:sup>\n                      medium containing DKK1) on the establishment, propagation, molecular features, and therapeutic responses of PDOs generated from malignant or non\u2010malignant gallbladder tissues derived from the same patient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both media supported successful PDO generation with comparable efficiency, preserving biliary epithelial functions and marker expression. Transcriptomic profiling confirmed selective enrichment of canonical Wnt target genes in PDOs generated in WNT\n                      <jats:sup>Act<\/jats:sup>\n                      cultures. WNT\n                      <jats:sup>Act<\/jats:sup>\n                      conditions enabled markedly superior long\u2010term propagation, whereas WNT\n                      <jats:sup>Inh<\/jats:sup>\n                      cultures more consistently retained the dysplastic features in malignant samples. Gemcitabine response assays demonstrated significantly greater drug sensitivity in PDOs grown in WNT\n                      <jats:sup>Act<\/jats:sup>\n                      medium, a phenotype reversible upon media switching but requiring extended adaptation, indicating a dynamic and context\u2010dependent influence of Wnt\u2010signaling on chemotherapeutic vulnerability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, the findings reveal a trade\u2010off between long\u2010term propagation and histological fidelity in gallbladder PDOs and show that Wnt\u2010signaling modulates gemcitabine sensitivity in a reversible manner. This comparative framework provides practical guidance for selecting culture conditions for gallbladder PDO\u2010based disease modeling, and precision oncology applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/boc.70074","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:02:57Z","timestamp":1782975777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Wnt Stimulation and Inhibition in the Development and Phenotype of Patient\u2010Derived Gallbladder Organoids"],"prefix":"10.1111","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9624-0305","authenticated-orcid":false,"given":"Ankita","family":"Dutta","sequence":"first","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"},{"name":"School of Medical Science and Technology Indian Institute of Technology  Kharagpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payel","family":"Guha","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshaya Vijayan","family":"Selvarajan","sequence":"additional","affiliation":[{"name":"TCS Research Tata Consultancy Services  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6783-9398","authenticated-orcid":false,"given":"Nandita","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritha","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrabanti Sarkar","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana Kumari","family":"Shaw","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debdutta","family":"Ganguli","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Sunderam","sequence":"additional","affiliation":[{"name":"TCS Research Tata Consultancy Services  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3546-2451","authenticated-orcid":false,"given":"Manas Kumar","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepatobiliary Surgery Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepatobiliary Surgery Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajgopal","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"TCS Research Tata Consultancy Services  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paromita","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Pathology Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2916-9649","authenticated-orcid":false,"given":"Vaskar","family":"Saha","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"},{"name":"Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"},{"name":"Division of Cancer Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindita","family":"Dutta","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"},{"name":"Division of Cancer Sciences University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9025-9547","authenticated-orcid":false,"given":"Dwijit","family":"GuhaSarkar","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.082"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010020\u201000474\u20101"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/boc.202400132"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","unstructured":"Dutta A. 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V.Selvarajan et\u00a0al.2026. \u201cAn Annotated Living Organoid Biobank for Studying Gallbladder Diseases and Drug Responses.\u201dDigestive Diseases and Sciences.https:\/\/doi.org\/10.1007\/s10620\u2010026\u201009707\u2010x.","DOI":"10.1007\/s10620-026-09707-x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.050"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31252"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.088"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4360"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07935"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01911\u201020"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010019\u20100168\u20100"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525\u2010022\u201000342\u20109"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.678"}],"container-title":["Biology of the Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/boc.70074","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/boc.70074","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/boc.70074","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:22:55Z","timestamp":1785165775000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/boc.70074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/boc.70074"],"URL":"https:\/\/doi.org\/10.1111\/boc.70074","archive":["Portico"],"relation":{},"ISSN":["0248-4900","1768-322X"],"issn-type":[{"value":"0248-4900","type":"print"},{"value":"1768-322X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70074"}}