The relationship between aging and cancer revealed by the mechanism of McSC fate determination

• Project/Area Number: 18K15114
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: The University of Tokyo (2021); Tokyo Medical and Dental University (2018-2020)
• Principal Investigator: Mohri Yasuaki 東京大学, 医科学研究所, 助教 (00622995)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 色素幹細胞 / 毛包幹細胞 / ニッチ / 白髪 / メラノーマ / 老化 / 皮膚

Outline of Final Research Achievements

Tissue stem cells play important roles in tissue homeostasis, aging and cancer, yet it is not clear how stem cells govern the different tissue fates. Hair graying and hair loss are known as the typical aging phenotypes. Hair graying is caused by the exhaustion of McSCs, while melanoma develops due to abnormal proliferation of McSCs. In this study, using skin as a model, McSC niche has been clarified to have a significant impact on the tissue fate of hair graying and melanoma under aging and genomic stress.

Academic Significance and Societal Importance of the Research Achievements

加齢による組織変化は臓器ごとにそれぞれの特徴を有するが、大きくは萎縮と癌化の2つに分類される。しかし、加齢にともない組織や臓器の加齢変化が萎縮に向かうのか、あるいは発癌に向かうのか、その実体はほとんど明らかになっていない。本研究は、ゲノムストレスによる色素幹細胞の運命決定の仕組みを明らかにしたものである。今後、組織ごとの共通性や独自性が明らかとなり、組織老化の仕組みの理解が進むことが想定されるため学術的な意義は高い。また、この仕組みは治療法の開発へとつながることも期待され、社会的意義も高い。

Research Products

• [Journal Article] Obesity accelerates hair thinning by stem cell-centric converging mechanisms (2021)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi (2021)
  • Author(s): Eshiba Sally、Namiki Takeshi、Mohri Yasuaki、Aida Tomomi、Serizawa Naotaka、Shibata Takakazu、Morinaga Hironobu、Nanba Daisuke、Hiraoka Yuichi、Tanaka Kohichi、Miura Keiko、Tanaka Masaru、Uhara Hisashi、Yokozeki Hiroo、Saida Toshiaki、Nishimura Emi K.
  • Journal Title: Cell Reports Volume: 36 Issue: 5 Pages: 109492-109492
  • DOI: 10.1016/j.celrep.2021.109492
  • Peer Reviewed
• [Journal Article] Dynamic stem cell selection safeguards the genomic integrity of the epidermis (2021)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles. (2021)
  • Author(s): Matsumura H, Liu N, Nanba D, Ichinose S, Takada A, Kurata S, Morinaga H, Mohri Y, De Arcangelis A, Ohno S, Nishimura EK.
  • Journal Title: Nature Aging Volume: 1 Pages: 190-204
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Novel Mouse Model Demonstrates That Oncogenic Melanocyte Stem Cells Engender Melanoma Resembling Human Disease (2019)
  • Author(s): Sun Q, Lee W, Mohri Y, Takeo M, Lim CH, Xu X, Myung P, Atit RP, Taketo MM, Moubarak RS, Schober M, Osman I, Gay DL, Saur D, Nishimura EK, Ito M.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 5023-5023
  • DOI: 10.1038/s41467-019-12733-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 加齢性の脱毛や白髪における 幹細胞の関与 (2021)
  • Author(s): ○毛利 泰彰、加藤 智起、芹澤 直隆、松村 寛行、森永 浩伸、西村 栄美
  • Organizer: 第20回日本抗加齢医学会総会
  • Invited
• [Presentation] Niche-derived KITL is essential for self-renewal of melanocyte stem cells under genotoxic stress. (2019)
  • Author(s): Yasuaki MOHRI, Tomoki KATO, Takahiro AOTO, Naotaka SERIZAWA, Emi K NISHIMURA
  • Organizer: 第29回日本色素細胞学会学術大会
• [Presentation] 色素幹細胞の老化と癌化 (2018)
  • Author(s): 毛利泰彰、青戸隆弘、難波大輔、松村寛之、森永浩伸、西村 栄美
  • Organizer: AMED老化第二回リトリート