Molecular characterization and prospective isolation of human fetal cochlear hair cell progenitors

Marta Roccio (), Michael Perny, Megan Ealy, Hans Ruedi Widmer, Stefan Heller and Pascal Senn
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Marta Roccio: University of Bern
Michael Perny: University of Bern
Megan Ealy: Stanford University School of Medicine
Hans Ruedi Widmer: Neurocenter and Regenerative Neuroscience Cluster, Inselspital Bern
Stefan Heller: Stanford University School of Medicine
Pascal Senn: University of Bern

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06334-7

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