title: Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation.
abstract: 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.
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J-R
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Tang
authors.affiliation: Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Otorhinolaryngology, the Sixth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: H-S
authors.initials: HS
authors.lastname: Shi
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: The Affiliated Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: X-D
authors.initials: XD
authors.lastname: Qian
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J-L
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: C-C
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, the Affiliated Wenling People's Hospital, Wenzhou Medical University, Wenling, Zhejiang, China.
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, the Sixth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: S-K
authors.initials: SK
authors.lastname: Yin
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Shao
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: T-S
authors.initials: TS
authors.lastname: Huang
authors.affiliation: Departments of Cell Biology and Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.affiliation: Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: M-X
authors.initials: MX
authors.lastname: Guan
authors.affiliation: Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J-F
authors.initials: JF
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D002675:Child, Preschool; D020405:Dermis / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D009154:Mutation; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000072636:PAX8 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C485245:MYO15A protein, human; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D014157:Transcription Factors; D009218:Myosins