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In particular, mutation of the gap junction beta 2 gene (GJB2), which encodes connexin (CX)26 protein, is the most frequent cause of hereditary deafness worldwide. We previously described an induction method to develop functional CX26 gap junction-forming cells from mouse-induced pluripotent stem cells (iPSCs) and generated in vitro models for GJB2-related deafness. However, functional CX26 gap junction-forming cells derived from human iPSCs or embryonic stem cells (ESCs) have not yet been reported. In this study, we generated human iPSC-derived functional CX26 gap junction-forming cells (iCX26GJCs), which have the characteristics of cochlear supporting cells. These iCX26GJCs had gap junction plaque-like formations at cell\u2013cell borders and co-expressed several markers that are expressed in cochlear supporting cells. Furthermore, we generated iCX26GJCs derived from iPSCs from two patients with the most common GJB2 mutation in Asia, and these cells reproduced the pathology of GJB2-related deafness. These in vitro models may be useful for establishing optimal therapies and drug screening for various mutations in GJB2-related deafness.<\/jats:p>","DOI":"10.1093\/hmg\/ddab097","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T11:07:51Z","timestamp":1620990471000},"page":"1429-1442","source":"Crossref","is-referenced-by-count":14,"title":["Modeling gap junction beta 2 gene-related deafness with human iPSC"],"prefix":"10.1093","volume":"30","author":[{"given":"Ichiro","family":"Fukunaga","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Oe","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Danzaki","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhisa","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazusaku","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 1138421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"2021071607002542300_ref1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1097\/GIM.0b013e3181d0d42b","article-title":"Connexin-26-associated deafness: phenotypic variability and progression of hearing loss","volume":"12","author":"Chan","year":"2010","journal-title":"Genet. 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