A Novel in vitro Model Delineating Hair Cell Regeneration and Neural Reinnervation in Adult Mouse Cochlea

Frontiers in Molecular Neuroscience

Neuroscience

Zheng-Yi Chen¹  Wei Wei¹  Yizhou Quan¹  Mingqian Huang¹  Yilai Shu²  Wenyan Li²  Huawei Li³ 

[1] Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, MA, United States;Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, United States;Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, MA, United States;Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, United States;ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China;Institutes of Biomedical Sciences, Fudan University, Shanghai, China;ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China;Institutes of Biomedical Sciences, Fudan University, Shanghai, China;

关键词: hair cell;    adult;    regeneration;    novel model;    cochlea;   

DOI  :  10.3389/fnmol.2021.757831

 received in 2021-08-12, accepted in 2021-12-07,  发布年份 2022

来源: Frontiers

【 摘 要 】

The study of an adult mammalian auditory system, such as regeneration, has been hampered by the lack of an in vitro system in which hypotheses can be tested efficiently. This is primarily due to the fact that the adult inner ear is encased in the toughest bone of the body, whereas its removal leads to the death of the sensory epithelium in culture. We hypothesized that we could take advantage of the integral cochlear structure to maintain the overall inner ear architecture and improve sensory epithelium survival in culture. We showed that by culturing adult mouse cochlea with the (surrounding) bone intact, the supporting cells (SCs) survived and almost all hair cells (HCs) degenerated. To evaluate the utility of the explant culture system, we demonstrated that the overexpression of Atoh1, an HC fate-determining factor, is sufficient to induce transdifferentiation of adult SCs to HC-like cells (HCLCs). Transdifferentiation-derived HCLCs resemble developmentally young HCs and are able to attract adult ganglion neurites. Furthermore, using a damage model, we showed that degenerated adult ganglions respond to regenerated HCLCs by directional neurite outgrowth that leads to HCLC-neuron contacts, strongly supporting the intrinsic properties of the HCLCs in establishing HCLC-neuron connections. The adult whole cochlear explant culture is suitable for diverse studies of the adult inner ear including regeneration, HC-neuron pathways, and inner ear drug screening.

【 授权许可】

Unknown   
Copyright © 2022 Li, Quan, Huang, Wei, Shu, Li and Chen.