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Elucidation of the mechanisms of hair graying : an approach for tissue ageing

Research Project

Project/Area Number 19679006
Research Category

Grant-in-Aid for Young Scientists (S)

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionTokyo Medical and Dental University (2008-2011)
Kanazawa University (2007)

Principal Investigator

NISHIMURA Emi  Tokyo Medical and Dental University, 難治疾患研究所, 教授 (70396331)

Project Period (FY) 2007 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥115,180,000 (Direct Cost: ¥88,600,000、Indirect Cost: ¥26,580,000)
Fiscal Year 2011: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
Fiscal Year 2010: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
Fiscal Year 2009: ¥21,710,000 (Direct Cost: ¥16,700,000、Indirect Cost: ¥5,010,000)
Fiscal Year 2008: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000)
Fiscal Year 2007: ¥27,950,000 (Direct Cost: ¥21,500,000、Indirect Cost: ¥6,450,000)
Keywords色素幹細胞 / ニツチ / 白髪 / 17型コラーゲン / TGF-β / 自己複製 / 毛包幹細胞 / 色素細胞 / 幹細胞 / 老化 / 毛包 / 加齢 / ニッチ / ゲノム損傷 / ATM / 分化
Research Abstract

今年度は、白髪の発症において鍵になる色素幹細胞がどのような自己複製制御を受けているのか、その仕組みとして、幹細胞周囲の微小環境ニッチに着目して研究を行った。ニッチによる細胞外からの幹細胞制御については、色素幹細胞のニッチが色素幹細胞の運命を優勢に決定することを現象として捉えてはいたが(Nishimura EK.et al., Nature, 2002.)、そのメカニズムについては明らかではなかった。我々は、今年度、色素幹細胞と隣接して毛包バルジ領域に存在する毛包幹細胞が、色素幹細胞にとっての機能的なニッチ細胞として働くこと(Tanimura S et al. Cell Stem Cell 2011)、毛包幹細胞の分泌するTGF-βが色素幹細胞に作用し、その未分化性維持と休止期の維持を促進することを明らかにした(Nishimuura EK et a1., Cell Stem Ce11, 2010)。毛包幹細胞が17型コラーゲンを高レベルで発現しており毛包幹細胞の幹細胞性を維持するという役割を持つと同時に、毛包幹細胞が色素幹細胞のニッチ細胞として機能するためにも必須であること、これらの役割により白髪と脱毛を抑えていることが判明した。また、色素幹細胞が休眠状態に入る際に、Bc12が生存に必須となるのは、ニッチ由来のTGF-βシグナルに抗して色素幹細胞が生存する必要があるためであることも同時に判明した。一方、メラノーマ細胞では、TGF-βシグナルに抵抗して生存増殖することも明らかになった。(Nishimura EK et al., Cell Stem Ce11, 2010)

Report

(5 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report   Self-evaluation Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (60 results)

All 2011 2010 2009 2008 2007 Other

All Journal Article (17 results) (of which Peer Reviewed: 8 results) Presentation (29 results) Book (7 results) Remarks (2 results) Patent(Industrial Property Rights) (5 results)

  • [Journal Article] Hair follicle stem cells provide a functional niche for melanocyte stemcells.2011

    • Author(s)
      Tnimura S, Nishimura EX., et al.
    • Journal Title

      Cell Stem Cell

      Volume: 8 Pages: 177-187

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Key Roles for Transforming Growth Factor B in Melanocyte Stem Cell Maintenance2010

    • Author(s)
      Nishimura EX., Fisher DE., et al
    • Journal Title

      Cell Stem Cell

      Volume: 6(2) Pages: 130-140

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic stem cells.2010

    • Author(s)
      Miura M, Yokota T., et al
    • Journal Title

      Int J Dev Biol.

      Volume: 54(1) Pages: 33-39

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Key roles for Transforming growth factor β inmelanocyte stem cell maintenance2010

    • Author(s)
      Nishimura EK, et al.
    • Journal Title

      Cell Stem Cell 5; 6(2)

      Pages: 130-40

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic stem cells2010

    • Author(s)
      Miura M, Nishimura EK, Yokota T., ほか3名
    • Journal Title

      Int J Dev Biol. 54 (1)

      Pages: 33-9

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Key roles for transforming growth factor Beta in melanocyte stem cell maintenance.2010

    • Author(s)
      Nishimura EK, Fisher DE., et al.
    • Journal Title

      Cell Stem Cell. 6(2)

      Pages: 130-140

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A stem cell-derived gene(Sddr)negatively regulates differentiation of embyronic stem cells.2010

    • Author(s)
      Miura M, Yokota T., et al.
    • Journal Title

      Int J Dev Biol. 54(1)

      Pages: 33-39

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation2009

    • Author(s)
      Inomata K, Aoto T, Binh NT, ほか8名 Nishimura EK.
    • Journal Title

      Cell. 137 (6)

      Pages: 1088-99

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Genotoxic stress abrogates renewal of melanocyte stem cell by triggering their differentiation.2009

    • Author(s)
      Inomata K, Nishimura EK., et al.
    • Journal Title

      Cell. 137(6)

      Pages: 1088-1099

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of PAX3 by TGF-beta modulates melanocyte viability2008

    • Author(s)
      Yang G, Li Y, Nishimura EK, Xin H, Zhou A, Guo Y, Dong L, Denning MF, Nickoloff BJ, Cui R.
    • Journal Title

      Mol Cell. 32 (4)

      Pages: 554-63

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Epistatic Connections between MITF and Endothelin signaling in Waardenburg Syndrome and other pigmentary disorders.2008

    • Author(s)
      Sato-Jin K^§, Nishimura E. K. ^§, Akasaka E, Huber W, Nakano H, Miller A, Du J, Wu M, Hanada K, Sawamura D, Fisher DE, Imokawa G.
    • Journal Title

      FASEB J. 22 (4)

      Pages: 1155-68

    • Related Report
      2009 Self-evaluation Report
  • [Journal Article] Epistatic Connections between MITF and Endothelin signaling in Waardenburg Syndrome and other pigmentary disorders.2008

    • Author(s)
      Sato-Jin, K, Nishimura E. K. Fisher, D. E., Imokawa, G.
    • Journal Title

      FASEB J. 22(4)

      Pages: 1155-1168

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 色素幹細胞2008

    • Author(s)
      西村栄美
    • Journal Title

      遺伝子医学Mook別册 進みつづける細胞移植治療の実際 上巻

      Pages: 110-114

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 皮膚の幹細胞2008

    • Author(s)
      西村栄美
    • Journal Title

      実験医学増刊 最先端の幹細胞研究

      Pages: 107-112

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Epistatic Connections between MITF and Endothelin signaling in Waardenburg Syndrome and other pigmentary disorders.2007

    • Author(s)
      Sato-Jin K, Nishimura E. K Fisher DE, and Imokawa G
    • Journal Title

      FASEB J. (Epub ahead of print)(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 色素幹細胞の維持と白髪のメカニズム2007

    • Author(s)
      西村 栄美
    • Journal Title

      細胞工学 26-5

      Pages: 501-506

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 組織の老化とは?-白髪と色素幹細胞の老化2007

    • Author(s)
      西村 栄美
    • Journal Title

      再生医療 6-4

      Pages: 344-349

    • Related Report
      2007 Annual Research Report
  • [Presentation] 毛包幹細胞による色素幹細胞の制御2011

    • Author(s)
      西村栄美
    • Organizer
      第10回日本再生医療学会総会
    • Place of Presentation
      京王プラザホテル、東京
    • Year and Date
      2011-03-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Melanocyte Stem Cell Maintenance and aging2010

    • Author(s)
      西村栄美
    • Organizer
      Cold Spring Harbor Asia Conferences
    • Place of Presentation
      Surhou Dhshu Lake, China
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 毛包における幹細胞と老化、ストレス2010

    • Author(s)
      西村栄美
    • Organizer
      第31回日本炎症・再生医学会シンポジウム
    • Place of Presentation
      京王プラザホテ・レ・東京
    • Year and Date
      2010-08-06
    • Related Report
      2010 Annual Research Report
  • [Presentation] ステムセルエイジングと老化2010

    • Author(s)
      西村栄美
    • Organizer
      iPS・ES・体性幹細胞Forum 2010~基礎研究から臨床応用・創薬研究へ~
    • Place of Presentation
      UDX Gallery(秋葉原UDX 4F)
    • Year and Date
      2010-06-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation in Mice2010

    • Author(s)
      西村栄美
    • Organizer
      ISSCR 8^<th> Annual Meeting
    • Place of Presentation
      San Fancisco, CA USA
    • Year and Date
      2010-06-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 色素幹細胞の品質管理とエイジング2010

    • Author(s)
      西村栄美
    • Organizer
      日本分子生物学会第10回春季シンポジウム
    • Place of Presentation
      ホテル松島大観荘、宮城
    • Year and Date
      2010-06-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 毛包における幹細胞の生業と白髪脱毛2010

    • Author(s)
      西村栄美
    • Organizer
      第62回日本細胞生物学会大会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-05-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] ステムセルエイジングと白髪のメカニズム2010

    • Author(s)
      西村栄美
    • Organizer
      第109回日本皮膚科学会総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-04-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 色素幹細胞の品質管理と老化2010

    • Author(s)
      西村栄美
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島国際会議場
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] ステムセルエイジングと白髪2010

    • Author(s)
      西村栄美
    • Organizer
      第9回Kumamoto Dermatological Academy
    • Place of Presentation
      ホテルニューオータニ熊本
    • Year and Date
      2010-03-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Why does our hair turn gray? JSPS/JHU/NIA-sponsored symposium (Baltimore, U.S.A)2010

    • Author(s)
      Emi Nishimura
    • Organizer
      Ageing vs. Regenerative Medicine: How Much Can Stem Cell Do?
    • Place of Presentation
      NIA, Baltimore, USA
    • Year and Date
      2010-02-19
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Why does our hair turn gray?2010

    • Author(s)
      西村栄美
    • Organizer
      JSPS/JHU/NIA-sponsored symposium : Ageing vs Regenerative Medicine : How can Stem Cells Do?
    • Place of Presentation
      JSPSワシントンセンター(ボルチモア/U.S.A.)
    • Year and Date
      2010-02-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 組織幹細胞の自己複製制御と発癌2010

    • Author(s)
      西村栄美
    • Organizer
      平成21年度5領域合同シンポジウム
    • Place of Presentation
      学術総合センター 一橋記念講堂
    • Year and Date
      2010-01-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] ゲノム損傷ストレスによる色素幹細胞の自己複製阻害機構についての解析2009

    • Author(s)
      西村栄美
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] ステムセルエイジングと白髪について2009

    • Author(s)
      西村栄美
    • Organizer
      第22回日本色素細胞学会総会 特別講演
    • Place of Presentation
      福岡
    • Year and Date
      2009-12-05
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] ステムセルエイジングと白髪について2009

    • Author(s)
      西村栄美
    • Organizer
      第22回日本色素細胞学会総会
    • Place of Presentation
      福岡電機ビル第2会議室
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] ステムセルエイジングと組織の老化2009

    • Author(s)
      西村栄美
    • Organizer
      金沢大学『がん幹細胞医学の創出事業』成果シンポジウム
    • Place of Presentation
      金沢大学
    • Year and Date
      2009-11-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] Nishimura : Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation2009

    • Author(s)
      Ken Inomata, ほか9名, Emi K.
    • Organizer
      The 7th Stem Cell Research Symposium
    • Year and Date
      2009-05-19
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation2009

    • Author(s)
      西村栄美
    • Organizer
      第7回幹細胞シンポジウム
    • Place of Presentation
      泉ガーデンギャラリー
    • Year and Date
      2009-05-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Nishimura : Hair follicle stem cells provide a COL17A1-dependent niche for melanocyte stem cells2009

    • Author(s)
      Shintaro Tanimura, ほか6名 Emi K.
    • Organizer
      The 7th Stem Cell Research Symposium
    • Year and Date
      2009-05-15
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] 色素幹細胞におけるステムセルエイジング2009

    • Author(s)
      西村栄美
    • Organizer
      再生医療学会 シンポジウム『ステムセルエイジング』
    • Place of Presentation
      東京
    • Year and Date
      2009-03-05
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Melanocyte stem cell maintenance and ageing2008

    • Author(s)
      Nishimura, E. K.
    • Organizer
      International Symposium on Regenerative Medicine Tenth Anniversary of Institute for Frontier Medical Sciences
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-12-04
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Hair graying,melanocyte stem cell and their niche2008

    • Author(s)
      Nishimura, E. K.
    • Organizer
      41^<st> Annual Meeting for the Japanese Society of Developmental Biologists
    • Place of Presentation
      Tokushima
    • Year and Date
      2008-05-30
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Mechanisms of melanocyte stem cell maintenance by their niche2008

    • Author(s)
      Nishimura, E. K.
    • Organizer
      International Investigative Dermatology 2008, Hair Research Symposium
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-05-13
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Mechanisms of melanocyte stem cell maintenance by their niche.2008

    • Author(s)
      西村栄美
    • Organizer
      International Investigative Dermatology 2008, Hair Research Symposium.
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2008-05-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] Roles of transforming growth factor beta in melanocyte stem cell renewal2008

    • Author(s)
      Nishimura, E.K., Suzuki, M., Igras, V., Inomata, K., Widlund, H., Du, J., Beermann, F., Roes, J. Miyachi, Y., Fisher, D. E.
    • Organizer
      Cojoint Meeting of XXth International Pigment Cell Conference (IPCC) & Vth International Melanoma Research Congress (IMRC)
    • Place of Presentation
      Sapporo
    • Year and Date
      2008-05-08
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Roles of transforming growth factor beta in melanocyte stem cell renewal.2008

    • Author(s)
      西村栄美
    • Organizer
      Cojoint Meeting of XXth International Pigment Cell Conference (IPCC) & Vth International Melanoma Research Congress (IMRC)
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2008-05-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] 色素幹細胞の運命と色素性疾患2007

    • Author(s)
      西村 栄美
    • Organizer
      第71回日本皮膚科学会東部支部学術大会
    • Place of Presentation
      ロイトと札幌
    • Year and Date
      2007-09-23
    • Related Report
      2007 Annual Research Report
  • [Presentation] 色素細胞の一生を追って2007

    • Author(s)
      西村 栄美
    • Organizer
      第106回日本皮膚科学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-04-20
    • Related Report
      2007 Annual Research Report
  • [Book] 実験医学2011

    • Author(s)
      西村栄美
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Book] 再生医療2010

    • Author(s)
      青戸隆博、西村栄美
    • Total Pages
      11
    • Publisher
      メデイカルレビュー社
    • Related Report
      2010 Annual Research Report
  • [Book] 医学のあゆみ2010

    • Author(s)
      青戸隆博、西村栄美
    • Total Pages
      2
    • Publisher
      医歯薬山版株式会社
    • Related Report
      2010 Annual Research Report
  • [Book] ファルマシア2010

    • Author(s)
      青戸隆博、西村栄美
    • Total Pages
      6
    • Publisher
      日本薬学会
    • Related Report
      2010 Annual Research Report
  • [Book] 最新医学(「毛包における幹細胞とそのニッチ」64 (通号806) 2009 (増刊))2009

    • Author(s)
      田所優子, 西村栄美
    • Related Report
      2009 Self-evaluation Report
  • [Book] 『色素幹細胞』遺伝子医学 Mook 別冊進みつづける細胞移植治療の実際上巻2008

    • Author(s)
      西村栄美
    • Publisher
      株式会社メディカルドゥ
    • Related Report
      2009 Self-evaluation Report
  • [Book] 実験医学(「皮膚の幹細胞」, 最先端の幹細胞研究(2008増刊)2008

    • Author(s)
      西村栄美
    • Related Report
      2009 Self-evaluation Report
  • [Remarks] 平成19年4月19日文部科学大臣表彰若手科学者賞受賞

    • Related Report
      2009 Self-evaluation Report
  • [Remarks] 本研究費による主要な研究成果 (左記文献#3) に対して、平成21年6月5白、東京医科歯科大学よりプレスリリース。テレビ取材を受け、NHKおはよう日本、スーパーニユースなどにて報道。新聞掲載多数 (読売新聞、朝日新聞、毎日新聞、日本経済新聞、東新聞掲載 : 日本経済新聞、東京新聞、日刊工業新聞など。)BBCニユースのほか、Bloomberg News など海外のメディア報道。

    • Related Report
      2009 Self-evaluation Report
  • [Patent(Industrial Property Rights)] 色素幹細胞の未分化性維持促進剤2009

    • Inventor(s)
      西村栄美
    • Industrial Property Rights Holder
      西村栄美
    • Industrial Property Number
      2009-244447
    • Filing Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] Methods for inhibiting hair depigmentation and hair loss2008

    • Inventor(s)
      西村栄美, ほか
    • Industrial Property Rights Holder
      金沢大学
    • Filing Date
      2008-02-22
    • Related Report
      2009 Self-evaluation Report
  • [Patent(Industrial Property Rights)] 脱毛の抑制方法および毛髪の脱色素化の抑制方法2008

    • Inventor(s)
      西村栄美, ほか
    • Industrial Property Rights Holder
      金沢大学
    • Filing Date
      2008-02-25
    • Related Report
      2009 Self-evaluation Report
  • [Patent(Industrial Property Rights)] XVII型コラーゲンに関する分化掬制剤2007

    • Inventor(s)
      西村 栄美清水 宏, ほか4名
    • Industrial Property Rights Holder
      金沢大学北海道大学
    • Industrial Property Number
      2007-202319
    • Filing Date
      2007-08-02
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] XVII型コラーゲンに関する脱毛抑制剤及び毛髪の脱色素化抑制剤2007

    • Inventor(s)
      清水 宏西村 栄美, ほか3名
    • Industrial Property Rights Holder
      北海道大学金沢大学
    • Industrial Property Number
      2007-218702
    • Filing Date
      2007-08-24
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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