Generating high-fidelity cochlear organoids from human pluripotent stem cells

Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by ge-netic 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.

Automated summary

Using 3D cultures of human pluripotent stem cells, researchers replicated the differentiation process of cochlear hair cells by modulating Sonic Hedgehog and WNT signaling. The resulting cells displayed characteristics consistent with both outer and inner hair cells in the cochlea. These findings suggest the development of a promising system to model the human auditory organ.