| RRC ID |
64998
|
| Author |
Fukunaga I, Oe Y, Danzaki K, Ohta S, Chen C, Shirai K, Kawano A, Ikeda K, Kamiya K.
|
| Title |
Modeling gap junction beta 2 gene-related deafness with human iPSC.
|
| Journal |
Hum Mol Genet
|
| Abstract |
There are >120 forms of non-syndromic deafness associated with identified genetic loci. 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-cell 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.
|
| Volume |
30(15)
|
| Pages |
1429-1442
|
| Published |
2021-7-9
|
| DOI |
10.1093/hmg/ddab097
|
| PII |
6276067
|
| PMID |
33997905
|
| MeSH |
Cochlea / metabolism
Connexin 26 / genetics
Connexin 26 / metabolism*
Connexins / genetics
Deafness / genetics*
Deafness / metabolism
Gap Junctions / genetics*
Hearing Loss, Sensorineural / genetics
Humans
Induced Pluripotent Stem Cells / metabolism
Models, Biological
Mutation
|
| IF |
5.101
|
| Resource |
| Human and Animal Cells |
201B7(HPS0063) |
