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Author Notes:

Correspondence: Jin-Fu Wang, Ph.D., Institute of Cell and Development, College of Life Sciences, Zi-Jin-Gang Campus of Zhejiang University, No. 866, Yuhangtang Road, Hangzhou, Zhejiang 310058, People’s Republic of China. Telephone: 86-571-8820-6592; E-Mail: wjfu@zju.edu.cn

Z.-H.T.: initial manuscript writing, experiment performance, data analysis and interpretation; J.-R.C., J.D., X.-D.Q., C.Z., J.-L.C., C.-C.W., and L.L.: experiment performance, data analysis and interpretation; J.Z., J.-Z.C., and T.-S.H.: collection and/or assembly of data;

H.-S.S. and S.-K.Y.: electrophysiological recording; P.C. and M.-X.G.: conception and design, experimental design, project progression monitoring, data analysis and interpretation;

J.-F.W.: conception and design, experimental design, project progression monitoring, data analysis and interpretation, final manuscript writing.

The authors indicate no potential conflicts of interest.

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Research Funding:

This study was supported by the grants from the National Basic Research Program of China (Grants 2012CB967902 and 2014CB541705), the National Development Program of Important Scientific Instruments (Grant 2013YQ030595),

the Strategically Guiding Scientific Special Project from Chinese Academy of Sciences (Grant XDA04020202-23), the Opening Foundation of the State Key Laboratory of Space Medicine Fundamentals and Application (Grant SMFA12K02),

the TZ-1 Application Program (Grant KYTZ01-0901-FB-003), and the Chinese National Science Foundation (Grant 81570932). We also thank Rui-Jian Zhu for help with karyotype analysis.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell & Tissue Engineering
  • Cell Biology
  • Human induced pluripotent stem cells
  • MYO7A
  • Deafness
  • Genetic correction
  • Inner ear hair cells
  • Rescue
  • Inner-ear development
  • Myosin-Viia gene
  • Stereociliary bundles
  • Transcription factors
  • Hearing impairment
  • Expression
  • Cochlea
  • Generation
  • Proteins
  • Mice

Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells

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Journal Title:

Stem Cells Translational Medicine

Volume:

Volume 5, Number 5

Publisher:

, Pages 561-571

Type of Work:

Article | Final Publisher PDF

Abstract:

The genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation. In the present study, iPSCs were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T; P-iPSCs), the asymptomatic father of the patient (MYO7A c.1184G>A mutation; CF-iPSCs), and a normal donor (MYO7AWT/WT; C-iPSCs). One of MYO7A mutation sites (c.4118C>T) in the P-iPSCs was corrected using CRISPR/Cas9. The corrected iPSCs (CP-iPSCs) retained cell pluripotency and normal karyotypes. Hair cell-like cells induced from CP-iPSCs showed restored organization of stereocilia-like protrusions; moreover, the electrophysiological function of these cells was similar to that of cells induced from C-iPSCs and CF-iPSCs. These results might facilitate the development of iPSC-based gene therapy for genetic disorders.

Copyright information:

© AlphaMed Press 2016.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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