Role of bone marrow microenvironment for erythropoiesis
Project/Area Number |
18K16107
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 骨髄微小環境 / 赤血球造血 / Nestin陽性細胞 / Notchシグナル / IL-6 / 局所炎症 / 造血微小環境 / 赤芽球分化 / マクロファージ / Nestin陽性間葉系細胞 / 赤芽球造血 / 間葉系幹細胞 |
Outline of Final Research Achievements |
The BM microenvironment supporting the hematopoiesis of each lineage has not remained unclear. In this research, we found that the Nestin-expressing cells in the bone marrow (BM) supported erythropoiesis in the BM specifically. The disruption of Notch signaling in Nestin-expressing cells impaired erythroid differentiation in the BM of the genetically modified mice. Additionally, in the BM of these mice, the erythroid-island-forming abilities of the macrophages were impaired. IL-6 hyperproduction was detected in these macrophages, and the anti-IL-6 receptor antibody could revert the impairment of erythropoiesis in the BM.
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Academic Significance and Societal Importance of the Research Achievements |
これまで骨髄における造血を支持する骨髄微小環境において各血球系統特異的な微小環境は明らかになっていなかった。本研究により骨髄微小環境構成細胞の一種であるNestin発現細胞特異的にNotchシグナルが欠損させた遺伝子改変マウスの骨髄で赤芽球造血が特異的に障害され、骨髄中の赤芽球島形成が障害され、赤芽球島を構成するマクロファージにおいてIL-6が過剰産生されていること、生体内における骨髄での赤芽球造血の障害が抗IL-6レセプター抗体の投与により改善することを示した。 赤芽球造血障害を起こす再生不良性貧血や骨髄異形成症候群などにおける病態解明、新規治療法の開発の端緒となる知見が得られたと考えている。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] VAV1 mutations contribute to development of T-cell neoplasms in mice2020
Author(s)
Fukumoto Kota、Sakata-Yanagimoto Mamiko、Fujisawa Manabu、Sakamoto Tatsuhiro、Miyoshi Hiroaki、Suehara Yasuhito、Nguyen Tran B.、Suma Sakurako、Yanagimoto Shintaro、Shiraishi Yuichi、Chiba Kenichi、Bouska Alyssa、Kataoka Keisuke、Ogawa Seishi、Iqbal Javeed、Ohshima Koichi、Chiba Shigeru
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Journal Title
Blood
Volume: 136
Pages: 3018-3032
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] トロンボポエチン受容体作動薬治療を受けた再生不良性貧血患者の骨髄細胞における遺伝子変異の検討2021
Author(s)
Tatsuhiro Sakamoto, Naoshi Obara, Yasuhito Nannya, Manabu Kusakabe1), Takayasu Kato1), Naoki Kurita1), Yasuhisa Yokoyama, Hidekazu Nishikii, Mamiko Sakata-Yanagimoto, Yuichi Hasegawa, Shigeru Chiba
Organizer
第82回日本血液学会学術集会
Related Report
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[Book] The Peripheral T‐Cell Lymphomas2021
Author(s)
Tatsuhiro Sakamoto, Mamiko Sakata-Yanagimoto, Owen A. O'Connor M.D., Ph.D.,Won Seog KimPier Luigi Zinzani M.D., Ph.D., et al.
Total Pages
392
Publisher
WILEY
ISBN
9781119671312
Related Report