Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model

Sensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is li...

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Main Authors: Mami Matsunaga, Tomoko Kita, Ryosuke Yamamoto, Norio Yamamoto, Takayuki Okano, Koichi Omori, Satoko Sakamoto, Takayuki Nakagawa
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2020.583994/full
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author Mami Matsunaga
Tomoko Kita
Ryosuke Yamamoto
Norio Yamamoto
Takayuki Okano
Koichi Omori
Satoko Sakamoto
Takayuki Nakagawa
author_facet Mami Matsunaga
Tomoko Kita
Ryosuke Yamamoto
Norio Yamamoto
Takayuki Okano
Koichi Omori
Satoko Sakamoto
Takayuki Nakagawa
author_sort Mami Matsunaga
collection DOAJ
description Sensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is limited, but the auditory epithelia of non-mammalian organisms retain the capacity for hair cell regeneration. In the avian basilar papilla (BP), supporting cells (SCs), which give rise to regenerated hair cells, are usually quiescent. Hair cell loss induces both direct transdifferentiation and mitotic division of supporting cells. Here, we established an explant culture model for hair cell regeneration in chick basilar papillae and validated it for investigating the initial phase of hair cell regeneration. The histological assessment demonstrated hair cell regeneration via direct transdifferentiation of supporting cells. Labeling with 5-ethynyl-2′-deoxyuridine (EdU) revealed the occurrence of mitotic division in the supporting cells at specific locations in the basilar papillae, while no EdU labeling was observed in newly generated hair cells. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, consistent with previous findings. Also, unbiased analyses of RNA sequencing data revealed novel genes and signaling pathways that may be related to the induction of supporting cell activation in the chick basilar papillae. These results indicate the advantages of our explant culture model of the chick basilar papillae for exploring the molecular mechanisms of hair cell regeneration.
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spelling doaj.art-100831a734cb41acb2517b9269e30f952022-12-22T03:01:36ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-11-011410.3389/fncel.2020.583994583994Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture ModelMami Matsunaga0Tomoko Kita1Ryosuke Yamamoto2Norio Yamamoto3Takayuki Okano4Koichi Omori5Satoko Sakamoto6Takayuki Nakagawa7Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanMedical Innovation Center, Kyoto University, Kyoto, JapanDepartment of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanSensorineural hearing loss is a common disability often caused by the loss of sensory hair cells in the cochlea. Hair cell (HCs) regeneration has long been the main target for the development of novel therapeutics for sensorineural hearing loss. In the mammalian cochlea, hair cell regeneration is limited, but the auditory epithelia of non-mammalian organisms retain the capacity for hair cell regeneration. In the avian basilar papilla (BP), supporting cells (SCs), which give rise to regenerated hair cells, are usually quiescent. Hair cell loss induces both direct transdifferentiation and mitotic division of supporting cells. Here, we established an explant culture model for hair cell regeneration in chick basilar papillae and validated it for investigating the initial phase of hair cell regeneration. The histological assessment demonstrated hair cell regeneration via direct transdifferentiation of supporting cells. Labeling with 5-ethynyl-2′-deoxyuridine (EdU) revealed the occurrence of mitotic division in the supporting cells at specific locations in the basilar papillae, while no EdU labeling was observed in newly generated hair cells. RNA sequencing indicated alterations in known signaling pathways associated with hair cell regeneration, consistent with previous findings. Also, unbiased analyses of RNA sequencing data revealed novel genes and signaling pathways that may be related to the induction of supporting cell activation in the chick basilar papillae. These results indicate the advantages of our explant culture model of the chick basilar papillae for exploring the molecular mechanisms of hair cell regeneration.https://www.frontiersin.org/articles/10.3389/fncel.2020.583994/fullatoh1basilar papillaregenerationhair cellsupporting celltransdifferentiation
spellingShingle Mami Matsunaga
Tomoko Kita
Ryosuke Yamamoto
Norio Yamamoto
Takayuki Okano
Koichi Omori
Satoko Sakamoto
Takayuki Nakagawa
Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model
Frontiers in Cellular Neuroscience
atoh1
basilar papilla
regeneration
hair cell
supporting cell
transdifferentiation
title Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model
title_full Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model
title_fullStr Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model
title_full_unstemmed Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model
title_short Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model
title_sort initiation of supporting cell activation for hair cell regeneration in the avian auditory epithelium an explant culture model
topic atoh1
basilar papilla
regeneration
hair cell
supporting cell
transdifferentiation
url https://www.frontiersin.org/articles/10.3389/fncel.2020.583994/full
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