RRC ID 51932
著者 Fukunaga I, Fujimoto A, Hatakeyama K, Aoki T, Nishikawa A, Noda T, Minowa O, Kurebayashi N, Ikeda K, Kamiya K.
タイトル In Vitro Models of GJB2-Related Hearing Loss Recapitulate Ca2+ Transients via a Gap Junction Characteristic of Developing Cochlea.
ジャーナル Stem Cell Reports
Abstract Mutation of the Gap Junction Beta 2 gene (GJB2) encoding connexin 26 (CX26) is the most frequent cause of hereditary deafness worldwide and accounts for up to 50% of non-syndromic sensorineural hearing loss cases in some populations. Therefore, cochlear CX26-gap junction plaque (GJP)-forming cells such as cochlear supporting cells are thought to be the most important therapeutic target for the treatment of hereditary deafness. The differentiation of pluripotent stem cells into cochlear CX26-GJP-forming cells has not been reported. Here, we detail the development of a novel strategy to differentiate induced pluripotent stem cells into functional CX26-GJP-forming cells that exhibit spontaneous ATP- and hemichannel-mediated Ca2+ transients typical of the developing cochlea. Furthermore, these cells from CX26-deficient mice recapitulated the drastic disruption of GJPs, the primary pathology of GJB2-related hearing loss. These in vitro models should be useful for establishing inner-ear cell therapies and drug screening that target GJB2-related hearing loss.
巻・号 7(6)
ページ 1023-1036
公開日 2016-12-13
DOI 10.1016/j.stemcr.2016.10.005
PII S2213-6711(16)30243-0
PMID 27840044
PMC PMC5161531
MeSH Animals Calcium / metabolism* Cells, Cultured Cochlea / embryology* Cochlea / metabolism* Connexin 26 / metabolism* Ectoderm / metabolism Extracellular Space / metabolism Gap Junctions / metabolism* Gap Junctions / ultrastructure Hearing Loss / metabolism* Induced Pluripotent Stem Cells / metabolism Mice Models, Biological* Protein Aggregates Transcription Factors / metabolism
IF 6.032
引用数 4
リソース情報
ヒト・動物細胞 iPS-MEF-Ng-178B-5(APS0002) iPS-MEF-Fb/Ng-440A-3(APS0003)