Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.
Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.
White
Patricia M
PM
Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 W. Third Street, Los Angeles, California 90057, USA.
Doetzlhofer
Angelika
A
Lee
Yun Shain
YS
Groves
Andrew K
AK
Segil
Neil
N
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology*; D018920:Coculture Techniques; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005434:Flow Cytometry; D006199:Hair Cells, Auditory, Inner / Q000166:cytology*; D051379:Mice; D009925:Organ of Corti / Q000166:cytology; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis
C493961:Cdkn1b protein, mouse; D020800:Receptor, Nerve Growth Factor; D050760:Cyclin-Dependent Kinase Inhibitor p27