Abstract
Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation. Their loss is irreversible in humans resulting in permanent hearing loss. The development of therapeutic interventions for hearing loss requires fundamental knowledge about similarities and potential differences between animal models and human development as well as the establishment of human cell based-assays. Here we analyze gene and protein expression of the developing human inner ear in a temporal window spanning from week 8 to 12 post conception, when cochlear hair cells become specified. Utilizing surface markers for the cochlear prosensory domain, namely EPCAM and CD271, we purify postmitotic hair cell progenitors that, when placed in culture in three-dimensional organoids, regain proliferative potential and eventually differentiate to hair cell-like cells in vitro. These results provide a foundation for comparative studies with otic cells generated from human pluripotent stem cells and for establishing novel platforms for drug validation.
Highlights
Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation
An indicator of prosensory domain (PSD) cell cycle exit is the onset of expression of the cyclin-dependent kinase inhibitor 1B (CDKN1B), known as p27Kip[13,16]
We show that the human cochlear duct follows an apical-tobasal gradient of cell cycle exit while hair cell differentiation follows a basal-to-apical gradient[7,16]
Summary
Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation. Utilizing surface markers for the cochlear prosensory domain, namely EPCAM and CD271, we purify postmitotic hair cell progenitors that, when placed in culture in three-dimensional organoids, regain proliferative potential and eventually differentiate to hair cell-like cells in vitro. These results provide a foundation for comparative studies with otic cells generated from human pluripotent stem cells and for establishing novel platforms for drug validation. Hearing in humans relies on mechanosensitive hair cells located in the organ of Corti Hair cells and their surrounding non-sensory supporting cells derive from SOX2+ progenitors within a region of the developing cochlear duct known as the prosensory domain (PSD)[1]. Our results provide insights in the development of the human inner ear and provide a method to purify and culture human hair cell progenitors and differentiate them in vitro to hair cell-like cells
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