Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation
| Autor: | 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 |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Cell Death & Differentiation. 23:1347-1357 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2016.16 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink