Temporal dynamic analysis of hematopoietic stem cells in bone marrow microenvironment
| Project/Area Number |
17H05086
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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.
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| 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。
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Report
(4 results)
Research Products
(52 results)
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[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
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Journal Title
Haematologica
Volume: 105
Issue: 3
Pages: 796-807
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Nat Commun.
Volume: 10
Issue: 1
Pages: 4869-4869
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Cancer Sci
Volume: 110
Issue: 12
Pages: 3695-3707
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Nature.
Volume: 571
Issue: 7763
Pages: 117-121
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Stem Cell Reports.
Volume: 11(4)
Issue: 4
Pages: 988-997
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Nat Commun
Volume: 9
Issue: 1
Pages: 2733-2733
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Exp Hematol
Volume: 63
Pages: 41-51
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Stem Cell Reports
Volume: 14
Issue: 3
Pages: 500-508
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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