Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation
- Resource Type
- Authors
- Jiyuan Chen; ZH Tang; HS Shi; Min-Xin Guan; P Chen; Jinfu Wang; Taosheng Huang; JZ Shao; JZ Chen; J Zheng; L Li; SK Yin; Jr Chen; CC Wang; XD Qian; J Ding; Chao Zhang
- Source
- Cell Death & Differentiation. 23:1347-1357
- Subject
- Male
0301 basic medicine
Hearing loss
Cellular differentiation
Induced Pluripotent Stem Cells
Cell
GATA3 Transcription Factor
Myosins
Gene mutation
Biology
Polymorphism, Single Nucleotide
PAX8 Transcription Factor
03 medical and health sciences
otorhinolaryngologic diseases
medicine
Humans
Inner ear
Induced pluripotent stem cell
Molecular Biology
Genetics
Original Paper
Hair Cells, Auditory, Inner
Base Sequence
integumentary system
Cell growth
PAX2 Transcription Factor
Cell Differentiation
Dermis
Cell Biology
Fibroblasts
Cellular Reprogramming
Pedigree
Cell biology
030104 developmental biology
medicine.anatomical_structure
Child, Preschool
Mutation
Female
sense organs
Hair cell
CRISPR-Cas Systems
medicine.symptom
Transcription Factors
- Language
- ISSN
- 1476-5403
1350-9047
Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.