PMID- 33997905
OWN - NLM
STAT- MEDLINE
DCOM- 20220325
LR  - 20220325
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 30
IP  - 15
DP  - 2021 Jul 9
TI  - Modeling gap junction beta 2 gene-related deafness with human iPSC.
PG  - 1429-1442
LID - 10.1093/hmg/ddab097 [doi]
AB  - 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.
CI  - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Fukunaga, Ichiro
AU  - Fukunaga I
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
FAU - Oe, Yoko
AU  - Oe Y
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
FAU - Danzaki, Keiko
AU  - Danzaki K
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
FAU - Ohta, Sayaka
AU  - Ohta S
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
FAU - Chen, Cheng
AU  - Chen C
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
FAU - Shirai, Kyoko
AU  - Shirai K
AD  - Department of Otolaryngology, Head and Neck Surgery, Tokyo Medical University, 
      Tokyo 1600023, Japan.
FAU - Kawano, Atsushi
AU  - Kawano A
AD  - Department of Otolaryngology, Head and Neck Surgery, Tokyo Medical University, 
      Tokyo 1600023, Japan.
FAU - Ikeda, Katsuhisa
AU  - Ikeda K
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
FAU - Kamiya, Kazusaku
AU  - Kamiya K
AD  - Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 
      1138421, Japan.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 127120-53-0 (Connexin 26)
SB  - IM
MH  - Cochlea/metabolism
MH  - Connexin 26/genetics/*metabolism
MH  - Connexins/genetics
MH  - Deafness/*genetics/metabolism
MH  - Gap Junctions/*genetics
MH  - Hearing Loss, Sensorineural/genetics
MH  - Humans
MH  - Induced Pluripotent Stem Cells/metabolism
MH  - Models, Biological
MH  - Mutation
EDAT- 2021/05/18 06:00
MHDA- 2022/03/26 06:00
CRDT- 2021/05/17 06:29
PHST- 2020/08/21 00:00 [received]
PHST- 2021/03/29 00:00 [revised]
PHST- 2021/03/31 00:00 [accepted]
PHST- 2021/05/18 06:00 [pubmed]
PHST- 2022/03/26 06:00 [medline]
PHST- 2021/05/17 06:29 [entrez]
AID - 6276067 [pii]
AID - 10.1093/hmg/ddab097 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2021 Jul 9;30(15):1429-1442. doi: 10.1093/hmg/ddab097.