Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration

Takahiro Wakasaki, Hiroaki Niiro, Siamak Jabbarzadeh-Tabrizi, Mitsuru Ohashi, Takashi Kimitsuki, Takashi Nakagawa, Shizuo Komune, Koichi Akashi

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

抄録

Background: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. Results: In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p=0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced. Conclusions: The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.

元の言語英語
記事番号64
ジャーナルBMC Neuroscience
18
発行部数1
DOI
出版物ステータス出版済み - 8 16 2017

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Inner Ear
Regeneration
Stem Cells
Saccule and Utricle
Alopecia
Genes
Chickens
Cell Proliferation
Laser Capture Microdissection
Neural Stem Cells
Cyclin D1
Cochlea
Aminoglycosides
Gene Expression Profiling
Bromodeoxyuridine
Population
Hearing
Reverse Transcription
Birds
Vertebrates

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

これを引用

Musashi-1 is the candidate of the regulator of hair cell progenitors during inner ear regeneration. / Wakasaki, Takahiro; Niiro, Hiroaki; Jabbarzadeh-Tabrizi, Siamak; Ohashi, Mitsuru; Kimitsuki, Takashi; Nakagawa, Takashi; Komune, Shizuo; Akashi, Koichi.

:: BMC Neuroscience, 巻 18, 番号 1, 64, 16.08.2017.

研究成果: ジャーナルへの寄稿記事

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abstract = "Background: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. Results: In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p=0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced. Conclusions: The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.",
author = "Takahiro Wakasaki and Hiroaki Niiro and Siamak Jabbarzadeh-Tabrizi and Mitsuru Ohashi and Takashi Kimitsuki and Takashi Nakagawa and Shizuo Komune and Koichi Akashi",
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AU - Jabbarzadeh-Tabrizi, Siamak

AU - Ohashi, Mitsuru

AU - Kimitsuki, Takashi

AU - Nakagawa, Takashi

AU - Komune, Shizuo

AU - Akashi, Koichi

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AB - Background: Hair cell loss in the cochlea is caused by ototoxic drugs, aging, and environmental stresses and could potentially lead to devastating pathophysiological effects. In adult mammals, hair cell loss is irreversible and may result in hearing and balance deficits. In contrast, nonmammalian vertebrates, including birds, can regenerate hair cells through differentiation of supporting cells and restore inner ear function, suggesting that hair cell progenitors are present in the population of supporting cells. Results: In the present study, we aimed to identify novel genes related to regeneration in the chicken utricle by gene expression profiling of supporting cell and hair cell populations obtained by laser capture microdissection. The volcano plot identified 408 differentially expressed genes (twofold change, p=0.05, Benjamini-Hochberg multiple testing correction), 175 of which were well annotated. Among these genes, we focused on Musashi-1 (MSI1), a marker of neural stem cells involved in Notch signaling, and the downstream genes in the Notch pathway. Higher expression of these genes in supporting cells compared with that in hair cells was confirmed by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry analysis demonstrated that MSI1 was mainly localized at the basal side of the supporting cell layer in normal chick utricles. During the regeneration period following aminoglycoside antibiotic-induced damage of chicken utricles, the expression levels of MSI1, hairy and enhancer of split-5, and cyclin D1 were increased, and BrdU labeling indicated that cell proliferation was enhanced. Conclusions: The findings of this study suggested that MSI1 played an important role in the proliferation of supporting cells in the inner ear during normal and damaged conditions and could be a potential therapeutic target in the treatment of vestibular defects.

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