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Composition and function of metabolites as hematopoietic stem cell niche factors

Research Project

Project/Area Number 18H02845
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionNational Center for Global Health and Medicine

Principal Investigator

Takubo Keiyo  国立研究開発法人国立国際医療研究センター, その他部局等, 生体恒常性プロジェクト長 (50502788)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords造血幹細胞 / 幹細胞ニッチ / 骨髄 / イメージング / メタボロミクス / in vivoイメージング
Outline of Final Research Achievements

In adult mammals, blood cells are produced in the bone marrow. The bone marrow contains a microenvironment called the "niche" in which hematopoietic stem cells (HSCs), a type of tissue stem cell, reside. The niche provides HSCs with factors that control their function, number, and fate. In this study, we focused on metabolites present in bone marrow as elements of the niche that act on HSCs, and investigated their composition, distribution, and effects on HSCs. In particular, we found that fatty acids bound to albumin are required for the maintenance of HSCs.

Academic Significance and Societal Importance of the Research Achievements

骨髄の造血幹細胞ニッチで作動している分子機構の解明は、われわれの全細胞の半分以上を占める血液細胞の産生機構を解き明かす。さらに造血器腫瘍、あるいは血液細胞が関わる様々な疾患の病態の理解と治療法開発に寄与すると考えられる。また、体外で代謝物も含めてニッチ環境を再現することで、造血幹細胞の培養や増幅が可能になり、血液疾患病態の再現や、再生医療に利用可能な細胞ソースの供給にも貢献しうる。

Report

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

    (15 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 11 results) Remarks (1 results)

  • [Int'l Joint Research] Imperial College London(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] OGT Regulates Hematopoietic Stem Cell Maintenance via PINK1-Dependent Mitophagy2021

    • Author(s)
      Murakami Koichi、 ... 、Takubo Keiyo、Okamoto Shinichiro、Tamura Tomohiko、Nakajima Hideaki
    • Journal Title

      Cell Reports

      Volume: 34 Issue: 1 Pages: 108579-108579

    • DOI

      10.1016/j.celrep.2020.108579

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UTX maintains functional integrity of murine hematopoietic system by globally regulating aging-associated genes.2021

    • Author(s)
      Sera Y; Nakata Y; Ueda T; Yamasaki N; Koide S; Kobayashi H; Ikeda KI; Kobatake K; Iwasaki M; Oda H; Wolff L; Kanai A; Nagamachi A; Inaba T; Sotomaru Y; Ichinohe T; Koizumi M; Miyakawa Y; Honda ZI; Iwama A; Suda T; Takubo K; Honda H
    • Journal Title

      Blood.

      Volume: 137 Issue: 7 Pages: 908-922

    • DOI

      10.1182/blood.2019001044

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protocol for the Maintenance of Quiescent Murine Hematopoietic Stem Cells2020

    • Author(s)
      Kobayashi Hiroshi、Takubo Keiyo
    • Journal Title

      STAR Protocols

      Volume: 1 Issue: 2 Pages: 100078-100078

    • DOI

      10.1016/j.xpro.2020.100078

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph+ B cells but not bone marrow stem/progenitors2020

    • Author(s)
      Daiki Karigane, Hidenori Kasahara, ... , Keiyo Takubo.
    • Journal Title

      Leukemia & Lymphoma

      Volume: 62 Issue: 3 Pages: 679-687

    • DOI

      10.1080/10428194.2020.1837366

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-chain fatty acids bind to apoptosis-associated speck-like protein to activate inflammasome complex to prevent Salmonella infection2020

    • Author(s)
      Tsugawa Hitoshi、Kabe Yasuaki、Kanai Ayaka、Sugiura Yuki、Hida Shigeaki、Taniguchi Shun’ichiro、Takahashi Toshio、Matsui Hidenori、Yasukawa Zenta、Itou Hiroyuki、Takubo Keiyo、Suzuki Hidekazu、Honda Kenya、Handa Hiroshi、Suematsu Makoto
    • Journal Title

      PLOS Biology

      Volume: 18 Issue: 9 Pages: 3000813-3000813

    • DOI

      10.1371/journal.pbio.3000813

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis2020

    • Author(s)
      Mikawa Takumi、Shibata Eri、Shimada Midori、Ito Ken、Ito Tomiko、Kanda Hiroaki、Takubo Keiyo、Lleonart Matilde E.、Inagaki Nobuya、Yokode Masayuki、Kondoh Hiroshi
    • Journal Title

      iScience

      Volume: 23 Issue: 7 Pages: 101306-101306

    • DOI

      10.1016/j.isci.2020.101306

    • NAID

      120006870881

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification and local manipulation of bone marrow vasculature during intravital imaging2020

    • Author(s)
      Morikawa Takayuki、Tamaki Shinpei、Fujita Shinya、Suematsu Makoto、Takubo Keiyo
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 6422-6422

    • DOI

      10.1038/s41598-020-63533-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium.2019

    • Author(s)
      5.Fukushima T, Tanaka Y, Hamey FK, Chang CH, Oki T, Asada S, Hayashi Y, Fujino T, Yonezawa T, Takeda R, Kawabata KC, Fukuyama T, Umemoto T, Takubo K, Takizawa H, Goyama S, Ishihama Y, Honda H, Gottgens B, Kitamura T.
    • Journal Title

      Cell Rep

      Volume: 29 Issue: 12 Pages: 4144-4158

    • DOI

      10.1016/j.celrep.2019.11.061

    • NAID

      120006892032

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Type I Interferon Delivery by iPSC-Derived Myeloid Cells Elicits Antitumor Immunity via XCR1+ Dendritic Cells.2019

    • Author(s)
      Tsuchiya N, Zhang R, Iwama T, Ueda N, Liu T, Tatsumi M, Sasaki Y, Shimoda R, Osako Y, Sawada Y, Kubo Y, Miyashita A, Fukushima S, Cheng Z, Nakaki R, Takubo K, Okada S, Kaneko S, Ihn H, Kaisho T, Nishimura Y, Senju S, Endo I, Nakatsura T, Uemura Y.
    • Journal Title

      Cell Rep.

      Volume: 29 Issue: 1 Pages: 162-175

    • DOI

      10.1016/j.celrep.2019.08.086

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses2019

    • Author(s)
      Nagai M、Noguchi R、Takahashi D、Morikawa T、Koshida K、Komiyama S、Ishihara N、Yamada T、Kawamura YI.、Muroi K、Hattori K、Kobayashi N、Fujimura Y、Hirota M、Matsumoto R、Aoki R、Tamura-Nakano M、Sugiyama M、Katakai T、Sato S、Takubo K、Dohi T、Hase K
    • Journal Title

      Cell

      Volume: 178 Issue: 5 Pages: 1072-1087

    • DOI

      10.1016/j.cell.2019.07.047

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo.2019

    • Author(s)
      Kobayashi H, Morikawa T, Okinaga A, Hamano F, Hashidate-Yoshida T, Watanuki S, Hishikawa D, Shindou H, Arai F, Kabe Y, Suematsu M, Shimizu T, Takubo K.
    • Journal Title

      Cell Reports

      Volume: 28 Issue: 1 Pages: 145-158

    • DOI

      10.1016/j.celrep.2019.06.008

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATP turnover and glucose dependency in hematopoietic stem/progenitor cells are increased by proliferation and differentiation2019

    • Author(s)
      Watanuki Shintaro、Kobayashi Hiroshi、Sorimachi Yuriko、Yamamoto Masamichi、Okamoto Shinichiro、Takubo Keiyo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 印刷中 Issue: 1 Pages: 287-294

    • DOI

      10.1016/j.bbrc.2019.04.123

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential involvement of semaphorin 3A in maintaining intervertebral disc tissue homeostasis2019

    • Author(s)
      Mima Y, Suzuki S, Fujii T, Morikawa T, Tamaki S, Takubo K, Shimoda M, Miyamoto T, Watanabe K, Matsumoto M, Nakamura M, Fujita N.
    • Journal Title

      J Orthop Res

      Volume: 37 Issue: 4 Pages: 972-980

    • DOI

      10.1002/jor.24258

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Remarks] 国立国際医療研究センター研究所生体恒常性プロジェクト公式ウェブサイト

    • URL

      https://takubolab.com/

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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