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Cochlear supporting cells as a target of cochlear pathology and regenerative medicine

Research Project

Project/Area Number 15K10749
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionKyoto University

Principal Investigator

Yamamoto Norio  京都大学, 医学研究科, 講師 (70378644)

Co-Investigator(Kenkyū-buntansha) 中川 隆之  京都大学, 医学研究科, 講師 (50335270)
坂本 達則  公益財団法人田附興風会, 医学研究所 第5研究部, 研究員 (60425626)
岡野 高之  京都大学, 医学研究科, 助教 (60642931)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords蝸牛支持細胞 / 成長因子 / 単一細胞 / 網羅的遺伝子解析 / 内耳 / IGF1 / Netrin1 / 支持細胞 / Unc5B / Sox2
Outline of Final Research Achievements

We performed two experiments. One is the comprehensive gene expression analysis from embryonic cochlear single cells. In this study, we picked up 47 Sox2-positive and 34 Sox2-negative cells and subjected these samples into microarray analysis. By filtering the acquired data to identify the probes that are expressed in the part of Sox2 -positive cells and none of the Sox2-negative cells, we got 28 probes. The gene that is represented by one of them was morphologically expressed in the part of the Sox2-positive region in the E13 inner ear. The other is the elucidation of the supporting cells-mediated cochlear hair cell protection mechanisms by IGF1. In this study, we identified that Netrin1, which is induced by IGF1 in supporting cells when treated with an aminoglycoside, protected cochlear hair cells through its receptor, Unc5B. This result indicates that supporting cells have important roles to protect hair cells from pharmacological injury.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (47 results)

All 2018 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (33 results) (of which Int'l Joint Research: 15 results,  Invited: 8 results)

  • [Journal Article] Netrin 1 mediates protective effects exerted by insulin-like growth factor 1 on cochlear hair cells.2017

    • Author(s)
      Yamahara K, Nakagawa T, Ito J, Kinoshita K, Omori K, Yamamoto N.
    • Journal Title

      Neuropharmacology.

      Volume: 119 Pages: 26-39

    • DOI

      10.1016/j.neuropharm.2017.03.032

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative Analysis of Aquaporin Expression Levels during the Development and Maturation of the Inner Ear2017

    • Author(s)
      Miyoshi, T. Yamaguchi, T. Ogita, K. Tanaka, Y. Ishibashi, K. I. Ito, H. Kobayashi, T. Nakagawa, T. Ito, J. Omori, K. Yamamoto, N.
    • Journal Title

      J Assoc Res Otolaryngol

      Volume: 18 Issue: 2 Pages: 247-261

    • DOI

      10.1007/s10162-016-0607-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of IGF1 Signaling in the Cochlea Induces the Transcription of Its Mediators During the Protection of Cochlear Hair Cells Against Aminoglycoside.2017

    • Author(s)
      Hayashi Y, Yamamoto N, Nakagawa T, Omori K, Ito J.
    • Journal Title

      Otol Neurotol.

      Volume: 38 Issue: 2 Pages: 278-282

    • DOI

      10.1097/mao.0000000000001276

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Histopathological evaluation and long-term results of soft tissue preservation technique in cholesteatoma surgery2017

    • Author(s)
      Hiraumi H., Kanemaru S. I., Miura M., Yamamoto N., Sakamoto T., and Ito J
    • Journal Title

      Eur Arch Otorhinolaryngol

      Volume: 274 Issue: 2 Pages: 711-714

    • DOI

      10.1007/s00405-016-4328-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Septin7 regulates inner ear formation at an early developmental stage.2016

    • Author(s)
      Torii H., Yoshida A., Katsuno T., Nakagawa T., Ito J., Omori K., Kinoshita M., and Yamamoto N
    • Journal Title

      Dev Biol

      Volume: 419 Issue: 2 Pages: 217-228

    • DOI

      10.1016/j.ydbio.2016.09.012

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The sensitivity and accuracy of a cone beam CT in detecting the chorda tympani2016

    • Author(s)
      Hiraumi, H. Suzuki, R. Yamamoto, N. Sakamoto, T. Ito, J.
    • Journal Title

      Eur Arch Otorhinolaryngol

      Volume: 273 Issue: 4 Pages: 873-877

    • DOI

      10.1007/s00405-015-3647-0

    • NAID

      120005944349

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition2016

    • Author(s)
      Taura, A. Taura, K. Koyama, Y. Yamamoto, N. Nakagawa, T. Ito, J. Ryan, A. F.
    • Journal Title

      Gene Ther

      Volume: Online Issue: 5 Pages: 1-9

    • DOI

      10.1038/gt.2016.12

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transplantation of neurons derived from human iPS cells cultured on collagen matrix into guinea pig cochleae.2016

    • Author(s)
      Ishikawa M*, Ohnishi H*, Skerleva D, Sakamoto T, Yamamoto N, Hotta A, Ito J, Nakagawa T.
    • Journal Title

      J Tissue Eng Regen Med.

      Volume: in press Issue: 6 Pages: 1-13

    • DOI

      10.1002/term.2072

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of salvage treatment on hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic corticosteroids: A retrospective observational study2015

    • Author(s)
      Nakagawa, T. Yamamoto, M. Kumakawa, K. Usami, S. I. Hato, N. Tabuchi, K. Takahashi, M. Fujiwara, K. Sasaki, A. Komune, S. Yamamoto, N. Hiraumi, H. Sakamoto, T. Shimizu, A. Ito, J.
    • Journal Title

      Auris Nasus Larynx

      Volume: Online Issue: 5 Pages: 1-6

    • DOI

      10.1016/j.anl.2015.12.004

    • NAID

      130006880794

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method2015

    • Author(s)
      Ohnishi, H. Skerleva, D. Kitajiri, S. Sakamoto, T. Yamamoto, N. Ito, J. Nakagawa, T.
    • Journal Title

      Neurosci Lett

      Volume: 599 Pages: 49-54

    • DOI

      10.1016/j.neulet.2015.05.032

    • NAID

      120005663317

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells2015

    • Author(s)
      Yamahara, K. Yamamoto, N. Nakagawa, T. Ito, J.
    • Journal Title

      Hear Res

      Volume: 330 Pages: 2-9

    • DOI

      10.1016/j.heares.2015.04.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Outcome of Cochlear Implantation for Mitochondrial Disease Patients With Syndromic Hearing Loss2015

    • Author(s)
      Yamamoto, N. Okuyama, H. Hiraumi, H. Sakamoto, T. Matsuura, H. Ito, J.
    • Journal Title

      Otol Neurotol

      Volume: 36 Issue: 8 Pages: e129-e133

    • DOI

      10.1097/mao.0000000000000817

    • NAID

      120005676661

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 再生医療から見た音声言語医学の未来 再生医学から見た音声言語医学の未来 人工内耳と再生医療2015

    • Author(s)
      山本 典生, 伊藤 壽一
    • Journal Title

      音声言語医学

      Volume: 56 Pages: 213-218

    • Related Report
      2015 Research-status Report
  • [Journal Article] 科学技術の進歩と聴覚医学 再生医療技術の聴覚医学への応用2015

    • Author(s)
      山本典生
    • Journal Title

      Audiology Japan

      Volume: 58 Pages: 219-226

    • NAID

      130005124829

    • Related Report
      2015 Research-status Report
  • [Presentation] Netrin1 Mediates the Protection of Cochlear Hair Cells by IGF1 through its Canonical Receptor, UNC5B2018

    • Author(s)
      Yamamoto Norio , Yamahara Kohei , Nakagawa Takayuki , Kinoshita Kazuo , Omori Koichi , Ito Juichi
    • Organizer
      41st Annual ARO MidWinter Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Septin7 regulates apoptosis to achieve gross morphogenesis during the development of inner ears2017

    • Author(s)
      Yamamoto, Norio ;Torii, Hiroko ;Yoshida, Atsuhiro ;Katsuno, Tatsuya ;Nakagawa, Takayuki ;Ito, Juichi ;Kinoshita, Makoto ;Omori, Koichi
    • Organizer
      The 40th Annual ARO Midwinter Meeting
    • Place of Presentation
      Baltimore, MD, USA
    • Year and Date
      2017-02-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Septin7は内耳発生早期において内耳形態形成を制御する2017

    • Author(s)
      山本 典生 , 鳥居 紘子 , 吉田 充裕 , 中川 隆之 , 伊藤 壽一 , 大森 孝一
    • Organizer
      第118回日本耳鼻咽喉科学会通常総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IGF1の下流分子としてのNetrin1の蝸牛有毛細胞保護作用2017

    • Author(s)
      山本 典生 , 山原 康平 , 中川 隆之 , 伊藤 壽一 , 大森 孝一
    • Organizer
      第62回日本聴覚医学会総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Netrin1 mediates the protection of cochlear hair cells by IGF1 through its canonical receptor, UNC5B2017

    • Author(s)
      Yamamoto Norio , Yamahara Kohei , Nakagawa Takayuki , Ito Juichi , Omori Koichi
    • Organizer
      54th Workshop on Inner Ear Biology and Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 聴覚(再)獲得のための人工内耳~小児から高齢者まで~2017

    • Author(s)
      山本典生
    • Organizer
      京都大学耳鼻咽喉科・頭頸部外科 公開講座 ―高度難聴医療の最前線 人工内耳―
    • Place of Presentation
      京都市
    • Related Report
      2016 Research-status Report
  • [Presentation] 先天性外耳道閉鎖症に対する外耳道形成、鼓室形成術例2017

    • Author(s)
      山本典生 ;倉田馨介 ;岡野高之 ;山崎博司 ;大森 孝一
    • Organizer
      第126回日本耳鼻咽喉科学会京滋合同地方部会
    • Place of Presentation
      大津市
    • Related Report
      2016 Research-status Report
  • [Presentation] CI for elderly Japanese people2016

    • Author(s)
      Yamamoto, Norio
    • Organizer
      The first Cochlear Global Research Symposium
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      2016-10-31
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 人工内耳埋め込み術を施行したIncomplete partition type 3症例2016

    • Author(s)
      山本 典生 ;岡野 高之 ;石田 愛 ;近藤 香菜子 ;山口 忍 ;山崎 博司 ;大森 孝一
    • Organizer
      第61回日本聴覚医学会総会・学術講演会
    • Place of Presentation
      盛岡市
    • Year and Date
      2016-10-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Effects of IGF1 to preserve hearing after CI electrode insertion2016

    • Author(s)
      Yamamoto, Norio
    • Organizer
      New Trends in Hearing Implant Sciences 2016 Hakuba meeting in OKUSHIGA -
    • Place of Presentation
      Shimotakai, Nagano
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蝸牛の単一細胞トランスクリトーム解析プロトコールの開発2016

    • Author(s)
      山本 典生 ;十名 洋介 ;中川 隆之 ;伊藤 壽一 ;大森 孝一
    • Organizer
      第26回日本耳科学会総会・学術講演会
    • Place of Presentation
      長野市
    • Year and Date
      2016-10-05
    • Related Report
      2016 Research-status Report
  • [Presentation] 人工内耳手術における移動式コーンビームCTの有用性2016

    • Author(s)
      山本 典生 ;坂本 達則 ;平海 晴一 ;岡野 高之 ;山崎 博司 ;伊藤 壽一 ;大森 孝一
    • Organizer
      第26回日本耳科学会総会・学術講演会
    • Place of Presentation
      長野市
    • Year and Date
      2016-10-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Single-cell Transcriptome Protocol of the Cochlear Development2016

    • Author(s)
      Yamamoto, Norio ;Tona, Yosuke ;Kita, Tomoko ;Ohnishi, Hiroe ;Nakagawa, Takayuki ;Omori, Koichi
    • Organizer
      53rd Inner Ear Biology Workshop
    • Place of Presentation
      Montpellier, France
    • Year and Date
      2016-09-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activation of IGF-1 Signaling in the Cochlea Induces the Transcription of its Mediators during the Protection of Cochlear Hair Cells against Aminoglycoside2016

    • Author(s)
      Yamamoto, Norio Search;Hayashi, Yushi Search;Nakagawa, Takayuki Search;Omori, Koichi Search;Ito, Juichi
    • Organizer
      American Neurotology Society 51st Annual Spring Meeting
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2016-05-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Netrin1受容体の蝸牛内における発現2016

    • Author(s)
      山原 康平 ;中川 隆之 ;伊藤 壽一 ;大森 孝一 ;山本 典生
    • Organizer
      第117回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      名古屋市
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Mobile Cone Beam CT Imaging during Cochlear Implantation Surgery2016

    • Author(s)
      Yamamoto, Norio ;Sakamoto, Tatsunori ;Hiraumi, Harukazu ;Ito, Juichi ;Okano, Takayuki ;Omori, Koichi
    • Organizer
      14th International Conference on Cochlear Implants and Other Implantable Technologies
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      2016-05-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mobile Cone Beam CT Imaging during Cochlear Implantation Surgery2016

    • Author(s)
      Yamamoto N, Sakamoto T, Hiraumi H, Ito J, Okano T, Omori K
    • Organizer
      16th Japan-Korea Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
    • Place of Presentation
      Hyatt Regency(Tokyo, Japan)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] IGF1とその下流シグナルによる内耳有毛細胞の保護・再生2016

    • Author(s)
      山本典生
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Single-cell Transcriptome Protocol of the Cochlear Development2016

    • Author(s)
      Yamamoto N, Tona Y, Nakagawa T, Ito J, Omori K
    • Organizer
      The 39th ARO MidWinter Meeting
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Netrin1受容体の蝸牛内における発現2016

    • Author(s)
      山原 康平 ;山本 典生 ;中川 隆之 ;伊藤 壽一
    • Organizer
      第34回耳鼻咽喉科ニューロサイエンス研究会
    • Place of Presentation
      大阪市
    • Related Report
      2016 Research-status Report
  • [Presentation] 耳科領域疾患の診断と治療2016

    • Author(s)
      山本 典生
    • Organizer
      平成28年度京都大学耳鼻咽喉科・頭頸部外科 病診・病病連携セミナー
    • Place of Presentation
      京都市
    • Related Report
      2016 Research-status Report
  • [Presentation] 耳科手術における術中cone beam CTの活用2016

    • Author(s)
      山本典生 ;坂本達則 ;平海晴一 ;伊藤壽一 ;岡野高之 ;大森孝一
    • Organizer
      第11回 耳鼻咽喉科3D断層画像研究会
    • Place of Presentation
      長野市
    • Related Report
      2016 Research-status Report
  • [Presentation] 転移性膿瘍形成を生じなかった感染性内頸静脈炎の1例2015

    • Author(s)
      山本典生
    • Organizer
      第2回京都小児科耳鼻咽喉科感染症フォーラム
    • Place of Presentation
      ハイアットリージェンシー京都(京都市)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] IGF1の下流分子、Netrin1による内耳有毛細胞保護効果2015

    • Author(s)
      山本 典生, 山原 康平, 中川 隆之, 伊藤 壽一
    • Organizer
      第25回日本耳科学会総会・学術講演会
    • Place of Presentation
      長崎ブリックホール(長崎市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Strategies for Induction of Regeneration in Mammalian Inner Ear2015

    • Author(s)
      Nakagawa T, Yamamoto N
    • Organizer
      52nd Inner Ear Biology Workshop
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The expression of Netrin1 receptors in sensory epithelium and spiral ganglion cells of the neonatal cochlea2015

    • Author(s)
      Yamamoto N, Yamahara K, Nakagawa T, Ito J
    • Organizer
      52nd Inner Ear Biology Workshop
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 人工内耳の歴史と未来2015

    • Author(s)
      山本典生
    • Organizer
      第7回関西みみはなのど治療研究会
    • Place of Presentation
      リーガロイヤルホテル(大阪市)
    • Year and Date
      2015-09-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 急性中耳炎ガイドラインについて2015

    • Author(s)
      山本典生
    • Organizer
      第29回洛筍会講演会
    • Place of Presentation
      京都センチュリーホテル(京都市)
    • Year and Date
      2015-07-30
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Labyrinthine fistulae due to cholesteatoma - validity of the classification evaluated by the CTP test2015

    • Author(s)
      Yamamoto N, Ikezono T, Hiraumi H, Sakamoto T, Ito J
    • Organizer
      30th Politzer Society Meeting
    • Place of Presentation
      TOKI MESSE(Niigata, Japan)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 耳科診療の進歩とこれから2015

    • Author(s)
      山本典生
    • Organizer
      京滋耳鼻咽喉科フォーラム
    • Place of Presentation
      ウェスティン都ホテル(京都市)
    • Year and Date
      2015-06-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] RS-EPI(Readout segmented echo-planer imaging)を用いた拡散強調画像による中耳真珠腫の診断2015

    • Author(s)
      山本典生 平海晴一 坂本達則 岡野高之 山崎博司 伊藤壽一
    • Organizer
      第116回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Presentation] ワークショップ 小児人工内耳適応基準(2014)をめぐって 小児人工内耳新適応基準における人工内耳手術の注意点2015

    • Author(s)
      山本典生
    • Organizer
      第10回日本小児耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      軽井沢プリンスホテル・ウエスト(長野県)
    • Year and Date
      2015-05-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Application of Insulin-Like Growth Factor-1 in the Treatment of Inner Ear Disorders2015

    • Author(s)
      Norio Yamamoto
    • Organizer
      2015 International Congress of Korean Society of Otorhinolaryngology-Head & Neck Surgery
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2015-04-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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