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Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells

Author

Listed:
  • Xiao-Ping Liu

    (F.M. Kirby Neurobiology Center Boston Children’s Hospital, and Harvard Medical School)

  • Karl R. Koehler

    (Indiana University School of Medicine)

  • Andrew M. Mikosz

    (Indiana University School of Medicine)

  • Eri Hashino

    (Indiana University School of Medicine)

  • Jeffrey R. Holt

    (F.M. Kirby Neurobiology Center Boston Children’s Hospital, and Harvard Medical School)

Abstract

Inner ear sensory epithelia contain mechanosensitive hair cells that transmit information to the brain through innervation with bipolar neurons. Mammalian hair cells do not regenerate and are limited in number. Here we investigate the potential to generate mechanosensitive hair cells from mouse embryonic stem cells in a three-dimensional (3D) culture system. The system faithfully recapitulates mouse inner ear induction followed by self-guided development into organoids that morphologically resemble inner ear vestibular organs. We find that organoid hair cells acquire mechanosensitivity equivalent to functionally mature hair cells in postnatal mice. The organoid hair cells also progress through a similar dynamic developmental pattern of ion channel expression, reminiscent of two subtypes of native vestibular hair cells. We conclude that our 3D culture system can generate large numbers of fully functional sensory cells which could be used to investigate mechanisms of inner ear development and disease as well as regenerative mechanisms for inner ear repair.

Suggested Citation

  • Xiao-Ping Liu & Karl R. Koehler & Andrew M. Mikosz & Eri Hashino & Jeffrey R. Holt, 2016. "Functional development of mechanosensitive hair cells in stem cell-derived organoids parallels native vestibular hair cells," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11508
    DOI: 10.1038/ncomms11508
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    Cited by:

    1. Jing Nie & Yoshitomo Ueda & Alexander J. Solivais & Eri Hashino, 2022. "CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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