{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:35:50Z","timestamp":1791959750859,"version":"4.3.4"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2700902"],"award-info":[{"award-number":["2021YFC2700902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030028"],"award-info":[{"award-number":["82030028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M692819"],"award-info":[{"award-number":["2021M692819"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sensorineural hearing loss often results from damaged or deficient inner ear hair cells. Mitochondrial 12S rRNA 1555A&amp;gt;G mutation has been associated with hearing loss in many families. The m.1555A&amp;gt;G mutation is a primary factor underlying the development of hearing loss and TRMU allele (c.28G&amp;gt;T, p.Ala10Sser) encoding tRNA thiouridylase interact with m.1555A&amp;gt;G mutation to cause hearing loss. However, the tissue specificity of mitochondrial dysfunction remains elusive and there is no highly effective therapy for mitochondrial deafness. We report here the generation of induced pluripotent stem cells (iPSCs) from lymphoblastoid cell lines derived from members of an Arab-Israeli family (asymptomatic individual carrying only m.1555A&amp;gt;G mutation, symptomatic individual bearing both m.1555A&amp;gt;G and c.28G&amp;gt;T mutations, and control subject). The c.28G&amp;gt;T mutation in iPSC lines from a hearing-impaired subject was corrected by CRISPR\/Cas9. These iPSCs were differentiated into otic epithelial progenitor (OEP) cells and subsequent inner ear hair cell (HC)-like cells. The iPSCs bearing m.1555A&amp;gt;G mutation exhibited mildly deficient differentiation into OEP and resultant HC-like cells displayed mild defects in morphology and electrophysiological properties. Strikingly, those HC-like cells harboring m.1555A&amp;gt;G and TRMU c.28G&amp;gt;T mutations displayed greater defects in the development, morphology and functions than those in cells bearing only m.1555A&amp;gt;G mutation. Transcriptome analysis of patients-derived HC-like cells revealed altered expressions of genes vital for mechanotransduction of hair cells. Genetic correction of TRMU c.28G&amp;gt;T mutation yielded morphologic and functional recovery of patient derived HC-like cells. These findings provide new insights into pathophysiology of maternally inherited hearing loss and a step toward therapeutic interventions for this disease.<\/jats:p>","DOI":"10.1093\/hmg\/ddac096","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T11:16:53Z","timestamp":1650539813000},"page":"3068-3082","source":"Crossref","is-referenced-by-count":23,"title":["Genetic correction of <i>TRMU<\/i> allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients"],"prefix":"10.1093","volume":"31","author":[{"given":"Chao","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomics , , Hangzhou, Zhejiang 310058 , China"},{"name":"The Children\u2019s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health , , Hangzhou, Zhejiang 310058 , China"},{"name":"Institute of Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310058 , China"},{"name":"Department of Human Genetics , , Hangzhou, Zhejiang 310058 , China"},{"name":"Zhejiang University School of Medicine , , Hangzhou, Zhejiang 310058 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-6736","authenticated-orcid":false,"given":"Min-Xin","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics , , Hangzhou, Zhejiang 310058 , China"},{"name":"The Children\u2019s Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health , , Hangzhou, Zhejiang 310058 , China"},{"name":"Institute of Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310058 , China"},{"name":"Department of Human Genetics , , Hangzhou, Zhejiang 310058 , China"},{"name":"Zhejiang University School of Medicine , , Hangzhou, Zhejiang 310058 , China"},{"name":"Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders , Hangzhou, Zhejiang 310058 China"},{"name":"Joint Institute of Genetics and Genomic Medicine between Zhejiang University and University of Toronto, Zhejiang University , Hangzhou, Zhejiang 310058 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"2022091511540255700_ref1","doi-asserted-by":"crossref","first-page":"a033258","DOI":"10.1101\/cshperspect.a033258","article-title":"The epidemiology of deafness","volume":"9","author":"Sheffield","year":"2018","journal-title":"Cold Spring Harb. 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