{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:50:26Z","timestamp":1791532226474,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H04764"],"award-info":[{"award-number":["JP21H04764"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24H02325"],"award-info":[{"award-number":["JP24H02325"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26H02362"],"award-info":[{"award-number":["JP26H02362"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ama121020"],"award-info":[{"award-number":["JP24ama121020"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24jf0126008h0001"],"award-info":[{"award-number":["24jf0126008h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mechanical cues influence cell behavior and fate and are frequently accompanied by changes in nuclear shape; however, how epithelial nuclei accommodate such deformations remains incompletely understood. In this article, we investigated the formation and regulation of nuclear wrinkles (NWs), inward folds of the nuclear envelope, in human epithelial cells. Using quantitative confocal imaging in 2.5D spheroid cultures and controlled 2D monolayers, we found that NWs formed frequently in MCF10A cells but rarely in hTERT\u2010RPE1 cells, indicating pronounced cell\u2010type specificity. NW frequency increased with cell density and was tightly associated with coordinated geometric changes consistent with nuclear rounding. Disruption of F\u2010actin organization, but not microtubules, robustly induced NW formation, and acute cell rounding triggered by trypsinization was sufficient to induce widespread wrinkling across multiple cell types. Live\u2010cell imaging revealed that NWs are dynamic and reversible at low cell density but become stabilized under sustained confinement. NW formation occurred without detectable nuclear envelope rupture, DNA damage, or stress\u2010associated histone phosphorylation. Quantitative analysis supports a passive geometric model in which redistribution of excess nuclear surface area accommodates nuclear shape remodeling, allowing epithelial nuclei to buffer mechanical constraints while preserving nuclear integrity.<\/jats:p>","DOI":"10.1111\/gtc.70152","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:20:42Z","timestamp":1791530442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nuclear Wrinkles Result From Geometric Adaptations to Cellular and Nuclear Morphological Changes in Epithelial Cells"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0020-8467","authenticated-orcid":false,"given":"Le Minh","family":"Khoa","sequence":"first","affiliation":[{"name":"School of Life Science and Technology Institute of Science Tokyo  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-9417","authenticated-orcid":false,"given":"Yohei","family":"Kono","sequence":"additional","affiliation":[{"name":"Nano Life Science Institute (WPI\u2010NanoLSI), Kanazawa University  Kanazawa Ishikawa Japan"},{"name":"Cell Biology Center Institute of Innovative Research, Tokyo Institute of Technology  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-1820","authenticated-orcid":false,"given":"Takeshi","family":"Shimi","sequence":"additional","affiliation":[{"name":"Nano Life Science Institute (WPI\u2010NanoLSI), Kanazawa University  Kanazawa Ishikawa Japan"},{"name":"Cell Biology Center Institute of Innovative Research, Tokyo Institute of Technology  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0854-083X","authenticated-orcid":false,"given":"Hiroshi","family":"Kimura","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology Institute of Science Tokyo  Yokohama Kanagawa Japan"},{"name":"Cell Biology Center Institute of Innovative Research, Tokyo Institute of Technology  Yokohama Kanagawa Japan"},{"name":"Cell Biology Center Institute of Integrated Research, Institute of Science Tokyo  Yokohama Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902035116"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.96.1.171"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200601060"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582\u20104934.2007.00176.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep01087"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120662"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200509124"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.173989"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1046\u20102023(03)00032\u2010x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.22.10065"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4SM00683F"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019103701"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13925"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.3.531"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0054"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200904137"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1667\/RR3308.2"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.11.009"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41567\u2010023\u201002216\u2010y"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432\u20100436.2003.7107003.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.190967"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010024\u201001476\u2010x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/b978\u20100\u201012\u2010394624\u20109.00007\u20105"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908686106"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.166330"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202201024"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.233700"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(91)90385\u2010c"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1513189113"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.03.008"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010bioeng\u2010060418\u2010052139"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511133103"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09\u2010151639"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1502111112"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010cellbio\u2010120319\u2010030049"},{"key":"e_1_2_11_38_1","doi-asserted-by":"crossref","unstructured":"Pachitariu M. M.Rariden andC.Stringer.2025.\u201cCellpose\u2010SAM: Superhuman Generalization for Cellular Segmentation.\u201d Preprint bioRxiv May 1.https:\/\/doi.org\/10.1101\/2025.04.28.651001.","DOI":"10.1101\/2025.04.28.651001"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201902046"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.6.1768"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746\u20104811\u201010\u201012"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195\u2010009\u20100057\u20107"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1735208"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594\u2010024\u201001286\u20107"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg273"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/19491034.2017.1414118"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260698"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21382"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep07362"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.5.1025"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201054577\u20104"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698\u2010024\u201000775\u20108"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.5.673"}],"container-title":["Genes to Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gtc.70152","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/gtc.70152","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gtc.70152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:20:45Z","timestamp":1791530445000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gtc.70152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":52,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/gtc.70152"],"URL":"https:\/\/doi.org\/10.1111\/gtc.70152","archive":["Portico"],"relation":{},"ISSN":["1356-9597","1365-2443"],"issn-type":[{"value":"1356-9597","type":"print"},{"value":"1365-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2026-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70152"}}