Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells
Abstract
Mammalian cochlear outer hair cells (OHCs) are essential for hearing. Severe hearing impairment follows OHC degeneration. Previous attempts at regenerating new OHCs from cochlear supporting cells (SCs) have been unsuccessful, notably lacking expression of the key OHC motor protein, Prestin. Thus, regeneration of Prestin+ OHCs represents a barrier to restore auditory function in vivo. Here, we reported the successful in vivo conversion of adult mouse cochlear SCs into Prestin+ OHC-like cells through the concurrent induction of two key transcriptional factors known to be necessary for OHC development: Atoh1 and Ikzf2. Single cell RNA sequencing revealed the upregulation of 729 OHC genes and downregulation of 331 SC genes in OHC-like cells. The resulting differentiation status of these OHC-like cells was much more advanced than previously achieved. This study thus established an efficient approach to induce the regeneration of Prestin+ OHCs, paving the way for in vivo cochlear repair via SC transdifferentiation.
Data availability
Sequencing data have been deposited in GEO under accession codes: GSE161156.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81771012)
- Zhiyong Liu
Ministry of Science and Technology of the People's Republic of China (2017YFA0103901)
- Zhiyong Liu
Chinese Academy of Sciences (XDB32060100)
- Zhiyong Liu
Shanghai Municipal Bureau of Quality and Technical Supervision (2018SHZDZX05)
- Zhiyong Liu
Shanghai Jiao Tong University (SSMU-ZLCX20180601)
- Zhiyong Liu
Boehringer Ingelheim (DE811138149)
- Zhiyong Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Doris K Wu, NIDCD, NIH, United States
Ethics
Animal experimentation: All mice were bred and raised in SPF level animal rooms and animal procedures were performed according to guidelines (NA-032-2019) of the IACUC of Institute of Neuroscience (ION), Chinese Academy of Sciences.
Version history
- Received: January 14, 2021
- Preprint posted: January 21, 2021 (view preprint)
- Accepted: September 2, 2021
- Accepted Manuscript published: September 3, 2021 (version 1)
- Version of Record published: September 14, 2021 (version 2)
Copyright
© 2021, Sun et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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