Chessum, L., Matern, M.S., Kelly, M.C. et al. (20 more authors) (2018) Helios is a key transcriptional regulator of outer hair cell maturation. Nature, 563 (7733). pp. 696-700. ISSN 0028-0836
Abstract
The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Springer Nature Limited. This is an author-produced version of a paper subsequently published in Nature. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 102892/Z/13/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 Jun 2019 14:17 |
Last Modified: | 14 Jun 2019 14:25 |
Status: | Published |
Publisher: | Nature Research |
Refereed: | Yes |
Identification Number: | 10.1038/s41586-018-0728-4 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:146863 |