Modulation of Wnt signaling enhances inner ear organoid development in 3D culture

Rachel E. De Jonge, Xiao Ping Liu, Christopher R. Deig, Stefan Heller, Karl R. Koehler, Eri Hashino

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles - a process that was previously self-organized by unknown mechanisms. The resulting otic-like vesicles have a larger lumen size and contain a greater number of Pax8/Pax2-positive otic progenitor cells than organoids derived without the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner ear organoids with hair cells whose morphological, biochemical and functional properties are indistinguishable from those of vestibular hair cells in the postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role during inner ear organoid formation as it does during inner ear development in the embryo.

Original languageEnglish (US)
Article numbere0162508
JournalPLoS One
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Organoids
Inner Ear
Stem cells
Cell culture
ears
Cells
Modulation
Tissue
Ear
Audition
Stem Cells
Epithelium
Vestibular Hair Cells
Dizziness
agonists
hairs
stem cells
Hearing Loss
epithelium
Embryonic Development

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

De Jonge, R. E., Liu, X. P., Deig, C. R., Heller, S., Koehler, K. R., & Hashino, E. (2016). Modulation of Wnt signaling enhances inner ear organoid development in 3D culture. PLoS One, 11(9), [e0162508]. https://doi.org/10.1371/journal.pone.0162508

Modulation of Wnt signaling enhances inner ear organoid development in 3D culture. / De Jonge, Rachel E.; Liu, Xiao Ping; Deig, Christopher R.; Heller, Stefan; Koehler, Karl R.; Hashino, Eri.

In: PLoS One, Vol. 11, No. 9, e0162508, 01.09.2016.

Research output: Contribution to journalArticle

De Jonge, Rachel E. ; Liu, Xiao Ping ; Deig, Christopher R. ; Heller, Stefan ; Koehler, Karl R. ; Hashino, Eri. / Modulation of Wnt signaling enhances inner ear organoid development in 3D culture. In: PLoS One. 2016 ; Vol. 11, No. 9.
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