Study of the regulation of hematopoietic stem cell self-renewal mediated by the control of actin polymerization
| Project/Area Number |
16K09824
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kanazawa University |
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Principal Investigator |
TADOKORO Yuko 金沢大学, がん進展制御研究所, 助教 (00447343)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 幹細胞 / 自己複製 / アクチン |
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| Outline of Final Research Achievements |
Interactions between tissue-specific stem cells and their microenvironment known as niche play important roles in the stem cell fate determination such as the maintenance, proliferation, and differentiation. In this study, we aim to elucidate the regulatory mechanisms of hematopoietic stem cell self-renewal mediated by the control of actin polymerization. In particular, we focused on the roles of Spred1, which is a negative regulator of ROCK and ERK signaling pathways, in hematopoietic stem cell (HSC) function. We have clearly shown that the control of actin polymerization mediated by Spred1-ROCK signaling pathway regulates the self-renewal capacity of HSCs. Furthermore, we have elucidated that Spred1 prevents high fat diet-induced tumorigenesis of HSCs through the regulation of ERK signaling pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
偏った食習慣は様々な疾患の原因になると考えられているが、幹細胞がどのような影響を受けるかについてはあまり知られていない。本研究成果においては、アクチン重合調節が造血幹細胞の自己複製制御に重要な役割を果たしていることを見出した点において学術的重要性がある。さらに、高脂肪食の状況下において造血幹細胞の白血病化の防御に働く因子としてSpred1を特定したことは、幹細胞機能の制御機構を理解する上で重要な知見である。またSpred1の発現低下は白血病発症や増悪化にも関わることから、食生活と白血病発症との関係を考える上で本研究成果の社会的意義は大きいと考えられる。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas.2018
Author(s)
Vu HT, Kobayashi M, Hegazy AM, Tadokoro Y, Ueno M, Kasahara A, Takase Y, Nomura N, Peng H, Ito C, Ino Y, Todo T, Nakada M, Hirao A
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Journal Title
Cancer Science
Volume: 109
Issue: 8
Pages: 2497-2508
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self-renewal of hematopoietic stem cells2018
Author(s)
Hui Peng, Atsuo Kasada, Masaya Ueno, Takayuki Hoshii, Yuko Tadokoro, Naho Nomura, Chiaki Ito, Yusuke Takase, Ha Thi Vu, Masahiko Kobayashi, Bo Xiao, Paul F. Worley, Atsushi Hirao
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 495
Issue: 1
Pages: 1129-1135
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.2016
Author(s)
Hegazy AM, Yamada D, Kobayashi M, Kohno S, Ueno M, Ali MA, Ohta K, Tadokoro Y, Ino Y, Todo T, Soga T, Takahashi C, Hirao A.
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Journal Title
J Biol Chem.
Volume: 291
Issue: 41
Pages: 21496-21509
DOI
Related Report
Peer Reviewed / Open Access
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