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Elucidation of the mechanisms for hair follicle aging focusing on stem cell divisions

Research Project

Project/Area Number 18H02637
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Matsumura Hiroyuki  東京医科歯科大学, 難治疾患研究所, 助教 (70581700)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords毛包幹細胞 / 幹細胞分裂 / 17型コラーゲン / aPKCλ / 老化 / 細胞極性 / ヘミデスモソーム
Outline of Final Research Achievements

Hair follicles, mammalian mini-organs that grow hair, miniaturize during aging, leading to hair thinning and loss. In this study, we revealed that hair follicle stem cells (HFSCs) lose their regenerative capabilities during aging owing to the adoption of an atypical cell division program. This type of division is accompanied by the destabilization of hemidesmosomal protein COL17A1 and cell polarity protein aPKCλ and generates terminally differentiating epidermal cells instead of regenerating the hair follicle niche. With the repetition of these atypical divisions, HFSCs detach from the basal membrane causing their exhaustion, elimination and organ aging. These results demonstrate that distinct stem cell division programs may govern tissue and organ aging.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、哺乳類の上皮系器官において再生と老化を担う幹細胞分裂プログラムの存在がはじめて明らかにした。これにより、加齢によって質の低下した幹細胞を効率よく生体から排除し、毛包自体も小型化し機能低下に至ることを世界に先駆けて解明した。また本成果は、器官の再生と老化の機序において幹細胞分裂がいかに中心的な役割を果たしうるかを明確に示すと同時に、加齢に伴う脱毛症の新規治療法開発やその他の上皮系臓器の加齢関連疾患の機構解明やその治療法開発にも繋がるものと期待される。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (28 results)

All 2021 2020 2019

All Journal Article (7 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 5 results) Book (8 results)

  • [Journal Article] Dynamic stem cell selection safeguards the genomic integrity of the epidermis2021

    • Author(s)
      Kato Tomoki、Liu Nan、Morinaga Hironobu、Asakawa Kyosuke、Muraguchi Taichi、Muroyama Yuko、Shimokawa Mariko、Matsumura Hiroyuki、Nishimori Yuriko、Tan Li Jing、Hayano Motoshi、Sinclair David A.、Mohri Yasuaki、Nishimura Emi K.
    • Journal Title

      Developmental Cell

      Volume: 56 Issue: 24 Pages: 3309-3320

    • DOI

      10.1016/j.devcel.2021.11.018

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis2021

    • Author(s)
      Nanba D, Toki F, Asakawa K, Matsumura H, Shiraishi K, Sayama K, Matsuzaki K, Toki H, Nishumura EK.
    • Journal Title

      J Cell Biol

      Volume: 220 Issue: 11

    • DOI

      10.1083/jcb.202012073

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Obesity accelerates hair thinning by stem cell-centric converging mechanisms2021

    • Author(s)
      Morinaga H, Mohri Y, Grachtchouk M, Asakawa K, Matsumura H, Oshima M, Takayama N, Kato T, Nishimori Y, Sorimachi Y,?Takubo K, Suganami T, Iwama A, Iwakura Y, Dlugosz AA, Nishimura EK.
    • Journal Title

      Nature

      Volume: 595 Issue: 7866 Pages: 266-271

    • DOI

      10.1038/s41586-021-03624-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles2021

    • Author(s)
      Matsumura H, Liu N, Nanba D, Ichinose S, Takada A, Kurata S, Morinaga H, Mohri Y, Adele De Arcangelis, Ohno S, Nishimura E K
    • Journal Title

      Nature Aging

      Volume: 1 Pages: 190-204

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] NUAK2 localization in normal skin and its expression in a variety of skin tumors with YAP2020

    • Author(s)
      Al-Busani Hind、Al-Sobaihi Saber、Nojima Kohei、Tanemura Atsushi、Yaguchi Tomonori、Kawakami Yutaka、Matsumura Hiroyuki、Nishimura Emi K.、Yokozeki Hiroo、Namiki Takeshi
    • Journal Title

      Journal of Dermatological Science

      Volume: 97 Issue: 2 Pages: 143-151

    • DOI

      10.1016/j.jdermsci.2020.01.008

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stem cell competition orchestrates skin homeostasis and ageing2019

    • Author(s)
      Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, Asakawa K, Morinaga H, Mohri Y, De Arcangelis A, Geroges-Labouesse E, Nanba D, Nishimura EK
    • Journal Title

      Nature

      Volume: 568(7752) Issue: 7752 Pages: 344-350

    • DOI

      10.1038/s41586-019-1085-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Beclin 1 regulates recycling endosome and is required for skin development in mice2019

    • Author(s)
      Noguchi Saori、Honda Shinya、Saitoh Tatsuya、Matsumura Hiroyuki、Nishimura Emi、Akira Shizuo、Shimizu Shigeomi
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 37-37

    • DOI

      10.1038/s42003-018-0279-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles2021

    • Author(s)
      松村 寛行○
    • Organizer
      第44回日本分子生物学会年会・ワークショップ
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 幹細胞分裂タイプの違いが毛包の再生と老化の運命を決定する2021

    • Author(s)
      松村 寛行○
    • Organizer
      第8回皮膚の会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Distinct stem cell division programs determine organ regeneration and aging in hair follicles2020

    • Author(s)
      Hiroyuki Matsumura○, Nan Liu, Daisuke Nanba, Shizuko Ichinose, Aki Takada, Sotaro Kurata, Hironobu Morinaga, Yasuaki Mohri, Adle De Arcangelis, Shigeo Ohno, Emi K. Nishimura
    • Organizer
      ESDR(European Society for Dermatological Research) 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles2020

    • Author(s)
      Hiroyuki Matsumura○, Nan Liu, Daisuke Nanba, Shizuko Ichinose, Aki Takada, Sotaro Kurata, Hironobu Morinaga, Yasuaki Mohri, Adle De Arcangelis, Shigeo Ohno, Emi K. Nishimura
    • Organizer
      ISSCR (International Society for Stem Cell Research) 2021 Virtual
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles2020

    • Author(s)
      Hiroyuki Matsumura○, Nan Liu, Daisuke Nanba, Shizuko Ichinose, Aki Takada, Sotaro Kurata, Hironobu Morinaga, Yasuaki Mohri, Adle De Arcangelis, Shigeo Ohno, Emi K. Nishimura
    • Organizer
      18th Stem Cell Research Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles2020

    • Author(s)
      松村 寛行○
    • Organizer
      2021年度東京医科歯科大学難治疾患研究所研究発表会, 最優秀論文賞発表
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 幹細胞競合が皮膚の恒常性維持と老化を司る:2019

    • Author(s)
      松村 寛行○
    • Organizer
      第42回日本分子生物学会年会・ワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 幹細胞ダイナミクスを中心とした皮膚老化機構の解明2019

    • Author(s)
      松村 寛行○
    • Organizer
      昭和大学学士会後援会セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Epidermal stem cell competition orchestrates skin homeostasis and ageing.2019

    • Author(s)
      Hiroyuki Matsumura○, Nan Liu, Tomoki Kato, Shizuko Ichinose, Aki Takada, Takeshi Namiki, Kyosuke Asakawa, Hironobu Morinaga, Yasuaki Mohri, Daisuke Nanba, Emi K. Nishimura:
    • Organizer
      ESDR 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Stem cell competition and division govern skin homeostasis and ageing.2019

    • Author(s)
      Hiroyuki Matsumura○, Nan Liu, Tomoki Kato, Shizuko Ichinose, Aki Takada, Takeshi Namiki, Kyosuke Asakawa, Hironobu Morinaga, Yasuaki Mohri, Daisuke Nanba, Emi K. Nishimura:
    • Organizer
      ISSCR 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 上皮系臓器の老化の仕組み:幹細胞競合が司る皮膚の恒常性と老化について2019

    • Author(s)
      松村 寛行○、劉 楠、西村栄美
    • Organizer
      第19回抗加齢医学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Stem cell competition and division govern skin homeostasis and ageing.2019

    • Author(s)
      Nan Liu, Hiroyuki Matsumura○, Tomoki Kato, Shizuko Ichinose, Aki Takada, Takeshi Namiki, Kyosuke Asakawa, Hironobu Morinaga, Yasuaki Mohri, Daisuke Nanba, Emi K. Nishimura
    • Organizer
      International skin conference Japan-Singapore.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Epidermal stem cell competition coupled with stem cell divisions in mammalian epidermis2019

    • Author(s)
      Nan Liu, Hiroyuki Matsumura○, Tomoki Kato, Daisuke Nanba, Emi K. Nishimura
    • Organizer
      Keystone Symposia 2019, Cell Competition in Development and Disease
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Book] 細胞個性に基づく幹細胞競合と皮膚再生・老化2021

    • Author(s)
      松村 寛行、西村 栄美
    • Total Pages
      5
    • Publisher
      月刊細胞、2021年9月号
    • Related Report
      2020 Annual Research Report
  • [Book] 幹細胞分裂タイプの違いが毛包の老化と再生を決定する2021

    • Author(s)
      松村 寛行、西村 栄美
    • Total Pages
      5
    • Publisher
      実験医学, 39(11),1757-1761(2021)
    • Related Report
      2020 Annual Research Report
  • [Book] 表皮幹細胞の細胞競合と皮膚の再生・老化2020

    • Author(s)
      松村 寛行、劉 楠、西村 栄美
    • Total Pages
      8
    • Publisher
      医学のあゆみ,274(5), 491-499,(2020) 細胞競合による生体制御とがん
    • Related Report
      2020 Annual Research Report
  • [Book] 幹細胞競合が皮膚の恒常性維持と老化を担う2020

    • Author(s)
      松村 寛行、劉 楠、西村 栄美
    • Total Pages
      2
    • Publisher
      医学のあゆみ,274(7),597-598,(2020)
    • Related Report
      2020 Annual Research Report
  • [Book] 細胞競合が担う皮膚の恒常性維持と老化2020

    • Author(s)
      松村 寛行、劉 楠、西村 栄美
    • Total Pages
      6
    • Publisher
      臨床皮膚科,74(5),37-43,(2020)「最近のトピックス2020」
    • Related Report
      2020 Annual Research Report
  • [Book] 医学のあゆみ、幹細胞競合が皮膚の恒常性維持と老化を担う2020

    • Author(s)
      松村 寛行、劉 楠、西村 栄美
    • Total Pages
      2
    • Publisher
      医歯薬出版
    • Related Report
      2019 Annual Research Report
  • [Book] 臨床皮膚科、細胞競合が担う皮膚の恒常性維持と老化2020

    • Author(s)
      松村 寛行、劉 楠、西村 栄美
    • Total Pages
      7
    • Publisher
      医学書院
    • Related Report
      2019 Annual Research Report
  • [Book] 再生医療、表皮幹細胞の細胞競合が担う皮膚の再生・老化2019

    • Author(s)
      劉 楠、松村 寛行、西村 栄美
    • Total Pages
      16
    • Publisher
      メディカルレビュー社
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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