Generation of innervated cochlear organoid recapitulates early development of auditory unit

Mingyu Xia; Jiaoyao Ma; Mingxuan Wu; Luo Guo; Yan Chen; Geng-lin Li; Shan Sun; Renjie Chai; Huawei Li; Wenyan Li

Stem Cell Reports (Jan 2023)

Generation of innervated cochlear organoid recapitulates early development of auditory unit

Mingyu Xia,
Jiaoyao Ma,
Mingxuan Wu,
Luo Guo,
Yan Chen,
Geng-lin Li,
Shan Sun,
Renjie Chai,
Huawei Li,
Wenyan Li

Affiliations

Mingyu Xia: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Jiaoyao Ma: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Mingxuan Wu: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Luo Guo: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Yan Chen: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Geng-lin Li: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Shan Sun: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
Renjie Chai: State Key Laboratory of Bioelectronics, Department of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, PR China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, PR China; Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, PR China; Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing 100069, PR China; Corresponding author
Huawei Li: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 20003, China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Centre of Cochlear Implant, Shanghai 200031, China; Corresponding author
Wenyan Li: 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 200031, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai 20003, China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Corresponding author

Journal volume & issue: Vol. 18, no. 1
pp. 319 – 336

Abstract

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Summary: Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral auditory circuity are still lacking. Here, we developed cochlear organoids with functional peripheral auditory circuity in a staging three-dimensional (3D) co-culture system by initially reprogramming cochlear progenitor cells (CPCs) with increased proliferative potency that could be long-term expanded, then stepwise inducing the differentiation of cochlear HCs, as well as the outgrowth of neurites from SGNs. The function of HCs and synapses within organoids was confirmed by a series of morphological and electrophysiological evaluations. Single-cell mRNA sequencing revealed the differentiation trajectories of CPCs toward the major cochlear cell types and the dynamic gene expression during organoid HC development, which resembled the pattern of native HCs. We established the cochlear organoids with functional synapses for the first time, which provides a platform for deciphering the mechanisms of sensorineural hearing loss.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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