• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Cellular Stress and Fate Determination in Melanocyte Stem Cells

Planned

Project AreaEstablishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging
Project/Area Number 26115003
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NISHIMURA Emi  東京医科歯科大学, 難治疾患研究所, 教授 (70396331)

Project Period (FY) 2014-07-10 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥137,280,000 (Direct Cost: ¥105,600,000、Indirect Cost: ¥31,680,000)
Fiscal Year 2018: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2017: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2016: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2015: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2014: ¥31,200,000 (Direct Cost: ¥24,000,000、Indirect Cost: ¥7,200,000)
Keywords幹細胞老化 / 幹細胞 / 再生 / 毛包 / 色素幹細胞 / 白髪 / 毛包幹細胞 / 脱毛 / 老化 / 分化 / ニッチ / 癌 / メラノーマ / 加齢 / ストレス
Outline of Final Research Achievements

Hair graying and hair thinning are prominent aging phenotypes, yet the underlying mechanisms have been elusive. We previously found that hair follicle stem cells (HFSCs) provide a functional niche for melanocyte stem cells (McSCs). In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes downregulation of type XVII collagen (COL17A1), a critical molecule for maintenance of HFSCs, to trigger HFSC aging and resultant hair follicle miniaturization. As COL17A1 is not expressed by McSCs but is critical for HFSCs to maintain McSCs, COL17A1 downregulation in HFSCs causes depletion of McSCs through their ectopic differentiation in the niche. The hair follicle aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ and indicating potential angles for anti-ageing therapeutic intervention.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、加齢性脱毛や白髪など典型的な老化形質の発現において組織幹細胞の加齢変化が中心的な役割を果たすこと、加齢によって品質の低下した幹細胞を効率よく生体から排除する仕組みが働くため幹細胞が枯渇し、その結果、器官自体が矮小化し、毛を生やしたり色素を沈着させるなどの機能が低下することを世界に先駆けて解明した。また本成果に基づく組織幹細胞の枯渇を防ぐ抗老化技術ならびに再生促進技術の開発は超高齢化社会において健康促進へと繋がるものと期待できる。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(38 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research Journal Article Presentation Book Remarks

  • [Int'l Joint Research] Harvard University(USA)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] p38α activates purine metabolism to initiate hematopoietic stem/progenitor cell cycling.2016

    • Author(s)
      Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K.
    • Journal Title

      Cell Stem Cell.

      Volume: 19 Pages: 192-204

    • DOI

      10.1016/j.stem.2016.05.013

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis2016

    • Author(s)
      Matsumura H, Mohri Y, Binh NT, Morinaga H, Fukuda M, Ito M, Kurata S, Hoeijmakers J, and Nishimura EK.
    • Journal Title

      Science

      Volume: 351(6273) Pages: 575-575

    • DOI

      10.1126/science.aad4395

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A Melanocyte-melanoma Precursor Niche in Sweat Glands of Volar Skin.2014

    • Author(s)
      Okamoto N, Aoto T, Uhara H, Yamazaki S, Akutsu H, Umezawa A, Nakauchi H, Miyachi Y, Saida T, Nishimura EK.
    • Journal Title

      Pigment Cell & Melanoma Research

      Volume: 27 Pages: 1039-1050

    • DOI

      10.1111/pcmr.12297

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Stem cells orchestrates hair follicle aging program2017

    • Author(s)
      Emi K. Nishimura
    • Organizer
      Joint Meeting of the German and Japanese Societies of Developmental Biologists
    • Place of Presentation
      Kiel, Germany
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 組織を支える幹細胞と微小環境(ニッチ)2017

    • Author(s)
      西村 栄美
    • Organizer
      千里ライフサイエンスセミナーK5
    • Place of Presentation
      千里ライフサイエンスセンタービル,大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechanisms of hair follicle aging2017

    • Author(s)
      西村 栄美
    • Organizer
      The 291st IMEG Seminar Tokyo Medical and Dental University-IMEG Joint Seminar
    • Place of Presentation
      熊本大学発生医学研究所,熊本
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 加齢による脱毛の仕組みから臓器の老化を考える2016

    • Author(s)
      西村 栄美
    • Organizer
      脳心血管抗加齢研究会2016
    • Place of Presentation
      秋葉原UDX, 東京
    • Year and Date
      2016-12-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 幹細胞制御と毛包の老化2016

    • Author(s)
      西村 栄美
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜, 神奈川
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Stem cells orchestrates hair follicle aging program2016

    • Author(s)
      西村 栄美
    • Organizer
      第27回CDBミーティング-Body Surface Tactics-
    • Place of Presentation
      理化学研究所 多細胞システム形成研究センター, 兵庫
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ニッチ由来のKITLは色素幹細胞の自己複製において必須である2016

    • Author(s)
      西村 栄美
    • Organizer
      第27回日本色素細胞学会総会
    • Place of Presentation
      岐阜大学サテライトキャンパス, 岐阜
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] Melanocyte stem cells in eccrine sweat glands : a potential origin of acral melanoma2016

    • Author(s)
      西村 栄美
    • Organizer
      第12回日独皮膚科学会
    • Place of Presentation
      軽井沢プリンスホテルウエスト, 長野
    • Year and Date
      2016-10-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] New Insights in Stem Cell Research & Age-related Changes in Skin and Hair Pigmentation2016

    • Author(s)
      Emi K. Nishimura
    • Organizer
      46th Annual ESDR Meeting
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織の老化プログラムとは?2016

    • Author(s)
      西村 栄美
    • Organizer
      Molecular Cardiovascular Conference Ⅱ 2016
    • Place of Presentation
      東京ドーム, 東京
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechanisms of hair follicle aging and hair loss2016

    • Author(s)
      Emi K. Nishimura
    • Organizer
      Cell Symposia:Aging and Metabolism 2016
    • Place of Presentation
      Melia Stges, Spain
    • Year and Date
      2016-07-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Environmentally induced extrinsic skin aging2016

    • Author(s)
      西村 栄美
    • Organizer
      JST・ライプニッツ協会共催ワークショップ”Healthy Ageng”
    • Place of Presentation
      有明がんセンター研究所, 東京
    • Year and Date
      2016-06-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 毛包の老化と幹細胞の運命制御2016

    • Author(s)
      西村 栄美
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ, 京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 色素幹細胞と皮膚の色素異常症2016

    • Author(s)
      西村 栄美
    • Organizer
      第115回日本皮膚科学会総会
    • Place of Presentation
      国立京都国際会館, 京都
    • Year and Date
      2016-06-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 毛包のエイジング2016

    • Author(s)
      西村 栄美
    • Organizer
      第24回毛髪科学研究会
    • Place of Presentation
      北九州国際会議場、福岡
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 組織、臓器の老化プログラム2016

    • Author(s)
      西村 栄美
    • Organizer
      第3回Geroscience Initiative Japan in Sendai~健康長寿を目指す老化医生物学~:
    • Place of Presentation
      東北大学医学部, 宮城
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Stem cell aging:a clue to understand hair thinning and graying2016

    • Author(s)
      Emi K. Nishimura
    • Organizer
      1st International Symposium on Stem Cell Aging and Disease
    • Place of Presentation
      東京大学伊藤ホール, 東京
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 色素幹細胞とメラノーマの発生2015

    • Author(s)
      西村 栄美
    • Organizer
      第26回日本色素細胞学会学術大会
    • Place of Presentation
      札幌医科大学講堂(北海道札幌市)
    • Year and Date
      2015-11-14
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] メラノーマの発生と色素幹細胞の運命制御2015

    • Author(s)
      西村 栄美
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 組織幹細胞の活性化とエイジング2015

    • Author(s)
      西村 栄美
    • Organizer
      第36回日本炎症・再生医学会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京)
    • Year and Date
      2015-07-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Melanocyte Stem Cells: a Key for Hair Graying and Melanoma2015

    • Author(s)
      Emi K. Nishimura
    • Organizer
      The 25th Annual Meeting of Korean Society for Investigative Dermatology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2015-03-27 – 2015-03-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 色素幹細胞と黒髪再生2015

    • Author(s)
      西村 栄美
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 皮膚の幹細胞システムと老化のメカニズム2014

    • Author(s)
      西村 栄美
    • Organizer
      第19回分生研シンポジウム
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2014-12-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Identification of Melanocyte Stem Cells and Melanocyte-melanoma Precursor Niche Glands2014

    • Author(s)
      Emi K. Nishimura
    • Organizer
      International Symposium on Tumor Biology in Kanazawa
    • Place of Presentation
      金沢東急ホテル(石川)
    • Year and Date
      2014-11-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 毛の再生と老化2014

    • Author(s)
      西村 栄美
    • Organizer
      第23回日本形成外科学会基礎学術集会
    • Place of Presentation
      キッセイ文化ホール(長野)
    • Year and Date
      2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Coupling of the Stress Sensitivity of Melanocyte Stem Cells to their Dormancy during a Hair Cycle2014

    • Author(s)
      Emi K. Nishimura
    • Organizer
      IPCC 2014
    • Place of Presentation
      Singapore, Singapore
    • Year and Date
      2014-07-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 皮膚幹細胞と毛髪再生:黒髪を再生できるか?2014

    • Author(s)
      西村 栄美
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      万国津梁館(沖縄)
    • Year and Date
      2014-07-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] 医学のあゆみ2016

    • Author(s)
      松村寛行, 西村栄美
    • Total Pages
      3
    • Publisher
      医歯薬出版
    • Related Report
      2016 Annual Research Report
  • [Book] 実験医学2016

    • Author(s)
      松村寛行, 毛利泰彰, 西村栄美
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Book] 癌と化学療法2014

    • Author(s)
      西村 栄美
    • Total Pages
      4
    • Publisher
      癌と化学療法社
    • Related Report
      2014 Annual Research Report
  • [Book] 実験医学2014

    • Author(s)
      毛利 泰彰、西村 栄美
    • Total Pages
      11
    • Publisher
      羊土社
    • Related Report
      2014 Annual Research Report
  • [Remarks] 国立大学法人 東京医科歯科大学難治疾患研究所幹細胞医学分野

    • URL

      http://www.tmd.ac.jp/mri/scm/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 平成27年度の業績のトピック:西村班員の毛包の老化に関する研究がScience誌に掲載されました

    • URL

      http://www.m.chiba-u.ac.jp/class/molmed/stemcellaging/research/index.html#04

    • Related Report
      2015 Annual Research Report
  • [Remarks] News & Topics: 論文がScienceに掲載されました

    • URL

      http://www.tmd.ac.jp/mri/scm/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-11-20   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi