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Temporal dynamic analysis of hematopoietic stem cells in bone marrow microenvironment

Research Project

Project/Area Number 17H05086
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

Yamazaki Satoshi  東京大学, 医科学研究所, 特任准教授 (50625580)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥22,620,000 (Direct Cost: ¥17,400,000、Indirect Cost: ¥5,220,000)
Fiscal Year 2019: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2017: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords造血幹細胞 / 骨髄微小環境 / 骨髄環境 / 3Dイメージング / 骨髄ニッチ / 時間的動態 / ニッチ
Outline of Final Research Achievements

Hematopoietic stem cells are one of the tissue stem cells that exist in the bone marrow and can supply all blood cells throughout the life of the body while remaining undifferentiated. By clarifying the dormancy mechanism of hematopoietic stem cells, the applicant demonstrated that TGF-beta is important for maintaining hibernation of hematopoietic stem cells. We also reported that activation of TGF-beta by Schwann cells in bone marrow induces dormancy of hematopoietic stem cells. In this project, based on the knowledge and experience that the applicant has reported so far, by analyzing the temporal dynamics of hematopoietic stem cells in the bone marrow microenvironment, we revealed a complex and complicated hematopoietic stem cell niche cell and its structure. We aimed to establish a foundation to establish a culture method for maintaining the undifferentiated state of hematopoietic stem cells in vitro.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は申請者がこれまでに蓄積してきた成果と技術をさらに洗練させ、骨髄微小環境における造血幹細胞の動態を時間的な軸を加えることにより、造血幹細胞が存在する骨髄微小環境の構造や構成している細胞の詳細をより鮮明にする。この造血幹細胞の未分化性を維持する微小環境の理解は、将来的に造血幹細胞を人工的に生体外で増幅する技術として不可欠であるとともに、白血病幹細胞などの血液疾患における新規治療法の確立にも重要であった。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (52 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (18 results) (of which Int'l Joint Research: 18 results,  Peer Reviewed: 18 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (31 results) (of which Int'l Joint Research: 5 results,  Invited: 31 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Stanford University(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] In vivo expansion of functional human hematopoietic stem progenitor cells by butyzamide.2020

    • Author(s)
      Sakurai M, Takemoto H, Mori T, Okamoto S, Yamazaki S.
    • Journal Title

      Int J Hematol.

      Volume: 111 Issue: 5 Pages: 739-741

    • DOI

      10.1007/s12185-020-02849-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Long-term ex vivo expansion of mouse hematopoietic stem cells2020

    • Author(s)
      Wilkinson AC, Ishida R, Nakauchi H, Yamazaki S
    • Journal Title

      Nat Protoc

      Volume: 15 Issue: 2 Pages: 628-648

    • DOI

      10.1038/s41596-019-0263-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo2020

    • Author(s)
      Ando M, Ando J, Yamazaki S, Ishii M, Sakiyama Y, Harada S, Honda T, Yamaguchi T, Nojima M, Ohshima K, Nakauchi H, Komatsu N
    • Journal Title

      Haematologica

      Volume: 105 Issue: 3 Pages: 796-807

    • DOI

      10.3324/haematol.2019.223511

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion2019

    • Author(s)
      Nishimura T, Hsu I, Martinez-Krams DC, Nakauchi Y, Majeti R, Yamazaki S, Nakauchi H, Wilkinson AC
    • Journal Title

      Exp Hematol

      Volume: 80 Pages: 16-20

    • DOI

      10.1016/j.exphem.2019.11.007

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antitumor immunity augments the therapeutic effects of p53 activation on acute myeloid leukemia.2019

    • Author(s)
      Hayashi Y, Goyama S, Liu X, Tamura M, Asada S, Tanaka Y, Fukuyama T, Wunderlich M, O'Brien E, Mizukawa B, Yamazaki S, Matsumoto A, Yamasaki S, Shibata T, Matsuda K, Sashida G, Takizawa H, Kitamura T.
    • Journal Title

      Nat Commun.

      Volume: 10 Issue: 1 Pages: 4869-4869

    • DOI

      10.1038/s41467-019-12555-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Akt inhibition synergizes with polycomb repressive complex 2 inhibition in the treatment of multiple myeloma.2019

    • Author(s)
      Rizk M, Rizq O, Oshima M, Nakajima-Takagi Y, Koide S, Saraya A, Isshiki Y, Chiba T, Yamazaki S, Ma A, Jin J, Iwama A, Mimura N.
    • Journal Title

      Cancer Sci

      Volume: 110 Issue: 12 Pages: 3695-3707

    • DOI

      10.1111/cas.14207

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bmi1 restricts the adipogenic differentiation of bone marrow stromal cells to maintain the integrity of the hematopoietic stem cell niche2019

    • Author(s)
      Kato Yuko、Hou Li-Bo、Miyagi Satoru、Nitta Eriko、Aoyama Kazumasa、Shinoda Daisuke、Yamazaki Satoshi、Kuribayashi Wakako、Isshiki Yusuke、Koide Shuhei、Si Sha、Saraya Atsunori、Matsuzaki Yumi、van Lohuizen Maarten、Iwama Atsushi
    • Journal Title

      Experimental Hematology

      Volume: 76 Pages: 24-37

    • DOI

      10.1016/j.exphem.2019.07.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation.2019

    • Author(s)
      Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H, Yamazaki S.
    • Journal Title

      Nature.

      Volume: 571 Issue: 7763 Pages: 117-121

    • DOI

      10.1038/s41586-019-1244-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mesenchymal-Epithelial Interactome Analysis Reveals Essential Factors Required for Fibroblast-Free Alveolosphere Formation2019

    • Author(s)
      Shiraishi Kazushige、Shichino Shigeyuki、Ueha Satoshi、Nakajima Takuya、Hashimoto Shinichi、Yamazaki Satoshi、Matsushima Kouji
    • Journal Title

      iScience

      Volume: 11 Pages: 318-333

    • DOI

      10.1016/j.isci.2018.12.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation.2018

    • Author(s)
      Hamanaka S, Umino A, Sato H, Hayama T, Yanagida A, Mizuno N, Kobayashi T, Kasai M, Suchy FP, Yamazaki S, Masaki H, Yamaguchi T, Nakauchi H.
    • Journal Title

      Stem Cell Reports.

      Volume: 11(4) Issue: 4 Pages: 988-997

    • DOI

      10.1016/j.stemcr.2018.08.015

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis2018

    • Author(s)
      Asada S, Goyama S, Inoue D, Shikata S, Takeda R, Fukushima T, Yonezawa T, Fujino T, Hayashi Y, Kawabata KC, Fukuyama T, Tanaka Y, Yokoyama A, Yamazaki S, Kozuka-Hata H, Oyama M, Kojima S, Kawazu M, Mano H, Kitamura T
    • Journal Title

      Nat Commun

      Volume: 9 Issue: 1 Pages: 2733-2733

    • DOI

      10.1038/s41467-018-05085-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The hematopoietic stem cell diet.2018

    • Author(s)
      Wilkinson AC, Yamazaki S.
    • Journal Title

      Int J Hematol.

      Volume: 107 Issue: 6 Pages: 634-641

    • DOI

      10.1007/s12185-018-2451-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hematopoietic insults damage bone marrow niche by activating p53 in vascular endothelial cells.2018

    • Author(s)
      Si S, Nakajima-Takagi Y, Iga T, Tsuji M, Hou L, Oshima M, Koide S, Saraya A, Yamazaki S, Takubo K, Kubota Y, Minamino T, Iwama A.
    • Journal Title

      Exp Hematol

      Volume: 63 Pages: 41-51

    • DOI

      10.1016/j.exphem.2018.04.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity.2018

    • Author(s)
      Wilkinson AC, Morita M, Nakauchi H, Yamazaki S.
    • Journal Title

      Exp Hematol.

      Volume: 63 Pages: 12-16

    • DOI

      10.1016/j.exphem.2018.04.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spred1 Safeguards Hematopoietic Homeostasis against Diet-Induced Systemic Stress2018

    • Author(s)
      Tadokoro Yuko、Hoshii Takayuki、Yamazaki Satoshi、Eto Koji、Ema Hideo、Kobayashi Masahiko、Ueno Masaya、Ohta Kumiko、Arai Yuriko、Hara Eiji、Harada Kenichi、Oshima Masanobu、Oshima Hiroko、Arai Fumio、Yoshimura Akihiko、Nakauchi Hiromitsu、Hirao Atsushi
    • Journal Title

      Cell Stem Cell

      Volume: 22 Issue: 5 Pages: 713-725

    • DOI

      10.1016/j.stem.2018.04.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In?Vivo Generation of Engraftable Murine Hematopoietic Stem Cells by Gfi1b, c-Fos , and Gata2 Overexpression within Teratoma2017

    • Author(s)
      Tsukada Masao、Ota Yasunori、Wilkinson Adam C.、Becker Hans J.、Osato Motomi、Nakauchi Hiromitsu、Yamazaki Satoshi
    • Journal Title

      Stem Cell Reports

      Volume: 9 Issue: 4 Pages: 1024-1033

    • DOI

      10.1016/j.stemcr.2017.08.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 1.An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.2017

    • Author(s)
      Ieyasu A, Ishida R, Kimura T, Morita M, Wilkinson AC, Sudo K, Nishimura T, Ohehara J, Tajima Y, Lai CY, Otsu M, Nakamura Y, Ema H, Nakauchi H, Yamazaki S
    • Journal Title

      Stem Cell Reports

      Volume: 14 Issue: 3 Pages: 500-508

    • DOI

      10.1016/j.stemcr.2017.01.015

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PhysiologicalSrsf2P95H expression causes impaired hematopoietic stem cell functions and aberrant RNA splicing in mice2017

    • Author(s)
      Kon Ayana、Yamazaki Satoshi、Nannya Yasuhito、Kataoka Keisuke、Ota Yasunori、Nakagawa Masahiro Marshall、Yoshida Kenichi、Shiozawa Yusuke、Morita Maiko、Yoshizato Tetsuichi、Sanada Masashi、Nakayama Manabu、Koseki Haruhiko、Nakauchi Hiromitsu、Ogawa Seishi
    • Journal Title

      Blood

      Volume: 131 Issue: 6 Pages: 621-635

    • DOI

      10.1182/blood-2017-01-762393

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 骨髄環境シグナルの理解と人工物による造血幹細胞制御2020

    • Author(s)
      山崎 聡
    • Organizer
      新学術(シンギュリラ×細胞ダイバース)合同ワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 無タンパク質培養系による造血幹細胞の増幅と維持2020

    • Author(s)
      山崎 聡
    • Organizer
      第4回理論免疫学ワークショップ
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞の増幅技術開発から応用へ2019

    • Author(s)
      山崎 聡
    • Organizer
      第57回バイオ・マイクロ・ナノテク特別研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Chemically-defined culture enables massive expansion of functional hematopoietic stem cells2019

    • Author(s)
      山崎 聡
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アミノ酸バランスと造血幹細胞制御2019

    • Author(s)
      山崎 聡
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞増幅技術を用いた応用と未来2019

    • Author(s)
      山崎 聡
    • Organizer
      PS細胞産学合同研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Long term ex vivo hematopoietic stem cell expansion2019

    • Author(s)
      山崎 聡
    • Organizer
      Hematology and Immunology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 造血幹細胞の増殖から応用へ2019

    • Author(s)
      山崎 聡
    • Organizer
      Expert meeting in Fukuoka
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞の増幅技術開発から見えてくる未来2019

    • Author(s)
      山崎 聡
    • Organizer
      第453回つくば分子生命科学セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞の増幅と応用2019

    • Author(s)
      山崎 聡
    • Organizer
      京都大学大学院教育コース「再生医療・臓器再建医学」リトリート
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞の未分化性維持と応用2019

    • Author(s)
      山崎 聡
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞の定量的な動態と機能解析方法の確立2019

    • Author(s)
      山崎 聡
    • Organizer
      細胞ダイバース 第五回領域会議 第四回公開シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 組織幹細胞の培養から再生医学へ2019

    • Author(s)
      山崎 聡
    • Organizer
      横浜市立大学講義
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨髄環境の理解と造血幹細胞制御2019

    • Author(s)
      山崎聡
    • Organizer
      第24回東海HSCT懇話会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Hematopoietic stem cell expansion using simple ex vivo condition2019

    • Author(s)
      山崎聡
    • Organizer
      新学術領域「細胞ダイバース」第2回若手ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Hematopoietic stem cell expansion by ex vivo2019

    • Author(s)
      山崎聡
    • Organizer
      2019US-Japan Symposium on Normal/Malignant Hematopoiesis and Novel Therapies for Hematologic Malignancies.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 培養条件をシンプルにすることによる造血幹細胞の理解2019

    • Author(s)
      山崎聡
    • Organizer
      第3回理論免疫学ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞の増幅技術開発と応用2018

    • Author(s)
      山崎聡
    • Organizer
      神戸再生医療勉強会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 骨髄環境の理解と造血肝細胞制御2018

    • Author(s)
      山崎聡
    • Organizer
      第11回先進血液学レクチャー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Understanding of bone marrow environment and hematopoietic stem cell regulateon2018

    • Author(s)
      山崎聡
    • Organizer
      日本血液学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 移植を用いない造血幹細胞の動態と機能解析方法の確立2018

    • Author(s)
      山崎聡
    • Organizer
      第28回日本サイトメトリー学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Valine starving permits hematopoietic stem cell transplantation without chemoirradiative myeloablation2017

    • Author(s)
      Satoshi Yamazaki
    • Organizer
      15th Stem Cell Research Symposium
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 造血幹細胞は生体内アミノ酸バランスに制御される2017

    • Author(s)
      山崎 聡
    • Organizer
      第15回先端血液学セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] In vivo generateon of hematopoietic stem cells from iPSCs through teratoma formation2017

    • Author(s)
      Satoshi Yamazaki
    • Organizer
      Canadian Institutes of Health Research and AMED joint Program in Epigenetics and Stem Cells meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 白血病治療に繋がる生体内アミノ酸バランス制御2017

    • Author(s)
      山崎 聡
    • Organizer
      第5回がんと代謝研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Optiming in vivo generateon of engratable murine hematopoietic stem cells from pluripotent stem cells through hemogenic endotheuum in teratomas2017

    • Author(s)
      Satoshi Yamazaki
    • Organizer
      The 3rd Africa International biotechnology and biomedical conference(AIBBC2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Induction of Hematopoietic Stem Cells from Teratoma2017

    • Author(s)
      Satoshi Yamazaki
    • Organizer
      The Jackson Laboratory Seminar
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Understanding of bone marrow environment and control of hematopoietic stem cells2017

    • Author(s)
      山崎 聡
    • Organizer
      The27th Hot Spring Harbor International Symposium
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨髄環境の理解と造血幹細胞制御2017

    • Author(s)
      山崎 聡
    • Organizer
      第38回セルセラピーセミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] デザイン生命工学―異種細胞間・異種階層間のコミュニケーションのデザインを目指して2017

    • Author(s)
      山崎 聡
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アミノ酸バランスが司る造血幹細胞の制御2017

    • Author(s)
      山崎 聡
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] ポリビニルカプロラクタム‐ポリビニル酢酸‐ポリエチレングリコールグラフトコポリマーを用いた造血幹細胞を含む免疫/血液細胞の増幅法2020

    • Inventor(s)
      山崎聡、渡部 素生
    • Industrial Property Rights Holder
      : 国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-010390
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] サイトカインを用いないヒト造血幹細胞増幅方法2019

    • Inventor(s)
      中内啓光、山崎聡、櫻井政寿、渡部 素生
    • Industrial Property Rights Holder
      : 国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-165470
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-23  

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