Letter | Published:

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells

Naturevolume 441pages984987 (2006) | Download Citation

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Abstract

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 cells1,2. 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 cells3 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 p27Kip1 (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

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Acknowledgements

We gratefully acknowledge S. Juntilla, J. Llamas and W. Makmura for animal care and genotyping; S. Chavira at the USC Flow Cytometry Section for FACS assistance, the Transgenic Mouse Core Facility at USC for generating the p27–GFP BAC transgenics, A. J. Hudspeth for the anti-espin antibody, T. Hasson for anti-myosin-VI and anti-myosin-VIIa, J. Johnson for Math1-GFP mice, J. Roberts for the p27Kip1-/- mice, and E. W. Rubel for helpful advice. This work was supported by grants from the Hair Cell Regeneration Initiative of the National Organisation for Hearing Research and from the NIH. P.M.W. was supported by an NIH training grant. Author contributions The project was conceived by A.K.G. and N.S.; experiments were planned, performed and analysed jointly by A.D. and P.M.W. with advice from A.K.G. and N.S. The p27–gfp transgenic mouse was constructed by Y.S.L.; the paper was written by A.D., A.K.G., N.S. and P.M.W.

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Author notes

  1. Patricia M. White and Angelika Doetzlhofer: *These authors contributed equally to this work

Affiliations

  1. Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 W. Third Street, California, 90057, Los Angeles, USA

    • Patricia M. White
    • , Angelika Doetzlhofer
    • , Yun Shain Lee
    • , Andrew K. Groves
    •  & Neil Segil
  2. Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033, USA

    • Andrew K. Groves
    •  & Neil Segil

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding authors

Correspondence to Andrew K. Groves or Neil Segil.

Supplementary information

  1. Supplementary Notes

    This file contains Supplementary Text, Supplementary Figures 1–3, Supplementary Table, Supplementary Methods and Supplementary Table. (PDF 1383 kb)

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https://doi.org/10.1038/nature04849

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