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) |