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: and . 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.
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http://dx.doi.org/10.7554/eLife.66547 | DOI Listing |
PLoS One
December 2023
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, United States of America.
Regeneration of mammalian cochlear hair cells (HCs) by modulating molecular pathways or transcription factors is a promising approach to hearing restoration; however, immaturity of the regenerated HCs in vivo remains a major challenge. Here, we analyzed a single cell RNA sequencing (scRNA-seq) dataset during Atoh1-induced supporting cell (SC) to hair cell (HC) conversion in adult mouse cochleae (Yamashita et al. (2018)) using multiple high-throughput sequencing analytical tools (WGCNA, SCENIC, ARACNE, and VIPER).
View Article and Find Full Text PDFElife
September 2021
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Nature
November 2018
Department of Otorhinolaryngology Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
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 tuning. 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.
View Article and Find Full Text PDFNeurosci Lett
November 2001
Section of Otolaryngology, Yale University School of Medicine, New Haven, CT 06510, USA.
The transmembrane motor protein prestin is thought to underlie outer hair cell (OHC) motility. Prestin expressed in non-auditory cells confers OHC-like electrical characteristics to the cell membrane, including the generation of gating-like currents (or non-linear capacitance), whose voltage dependence is susceptible to membrane tension and initial voltage conditions. Here we report that prestin's voltage sensitivity is, like that of the native motor, markedly temperature dependent.
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