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Generation of Standardized and Reproducible Forebrain-type Cerebral Organoids from Human Induced Pluripotent Stem Cells
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Generating high-fidelity cochlear organoids from human pluripotent stem cells.

Stephen T Moore1, Takashi Nakamura2, Jing Nie1

  • 1Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Cell Stem Cell
|July 7, 2023
PubMed
Summary

Scientists created human cochlear hair cells using stem cells. This breakthrough provides a new way to study hearing loss and the human auditory organ in vitro.

Keywords:
auditorycochleahair cellhumaninner earorganoidpluripotent stem cellscRNA-seq

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Area of Science:

  • Otoacoustic emissions
  • Stem cell biology
  • Auditory neuroscience

Background:

  • Mechanosensitive hair cells in the cochlea are crucial for hearing but are susceptible to damage.
  • Studying human cochlear hair cells is challenging due to the scarcity of tissue samples.
  • Organoids present a promising in vitro model for studying rare tissues like cochlear cells.

Purpose of the Study:

  • To replicate key differentiation cues for cochlear hair cell specification in vitro.
  • To develop a novel system for modeling the human auditory organ.
  • To investigate the role of specific signaling pathways in cochlear development.

Main Methods:

  • Utilized 3D cultures of human pluripotent stem cells.
  • Manipulated Sonic Hedgehog and WNT signaling pathways at specific times.
  • Analyzed gene expression and cellular morphology of developing otic progenitors.

Main Results:

  • Timed modulation of Sonic Hedgehog and WNT signaling induced ventral gene expression in otic progenitors.
  • Ventralized otic progenitors formed patterned epithelia containing hair cells.
  • Generated hair cells exhibited morphology, marker expression, and functional properties resembling both outer and inner cochlear hair cells.

Conclusions:

  • Early morphogenic cues are sufficient to drive cochlear induction.
  • This study establishes an unprecedented system for modeling the human auditory organ in vitro.
  • The developed system offers new possibilities for studying hearing loss and auditory organ development.