Generating high-fidelity cochlear organoids from human pluripotent stem cells

Stephen T. Moore, Takashi Nakamura, Jing Nie, Alexander J. Solivais, Isabel Aristizábal-Ramírez, Yoshitomo Ueda, Mayakannan Manikandan, V. Shweta Reddy, Daniel R. Romano, John R. Hoffman, Benjamin J. Perrin, Rick F. Nelson, Gregory I. Frolenkov, Susana M. Chuva de Sousa Lopes, Eri Hashino

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.

Original languageEnglish
Pages (from-to)950-961.e7
JournalCell Stem Cell
Volume30
Issue number7
DOIs
StatePublished - Jul 6 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

  • auditory
  • cochlea
  • hair cell
  • human
  • inner ear
  • organoid
  • pluripotent stem cell
  • scRNA-seq

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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