Back to Search Start Over

Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture.

Authors :
DeJonge, Rachel E.
Liu, Xiao-Ping
Deig, Christopher R.
Heller, Stefan
Koehler, Karl R.
Hashino, Eri
Source :
PLoS ONE. 9/8/2016, Vol. 11 Issue 9, p1-14. 14p.
Publication Year :
2016

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
11
Issue :
9
Database :
Academic Search Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
117952380
Full Text :
https://doi.org/10.1371/journal.pone.0162508