| Project/Area Number |
26461412
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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 | Kobe Shoin Women's University |
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Principal Investigator |
SATOH YUSUKE 神戸松蔭女子学院大学, 人間科学部, 准教授 (20506307)
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| Co-Investigator(Kenkyū-buntansha) |
石橋 知彦 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (30722285)
横田 貴史 大阪大学, 医学系研究科, 助教 (60403200)
織谷 健司 大阪大学, 医学系研究科, 准教授 (70324762)
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| Co-Investigator(Renkei-kenkyūsha) |
TANAKA HIROKAZU 近畿大学, 医学部, 講師 (40360846)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 造血幹細胞 / SATB1 / MS4A3 / 血球分化 |
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| Outline of Final Research Achievements |
We generated hematological-lineage restricted SATB1 conditional knock out (cKO) mice. Analyzing the adult bone marrow (BM) in these mice, we observed a significant decrease in the number of HSCs as compared to those in their wild type (WT) littermates. SATB1 cKO mice-derived HSCs showed lower BM reconstitution ability than WT HSCs. Next, we generated SATB1 reporter mice, and examined the early differentiation of HSCs. We found that the HSC fraction of adult BM consists of SATB1－ and SATB1+ cells. In transplantation experiments, the SATB1+ HSCs produced more lymphocytic cells and fewer myeloid cells in the recipients.
The membrane protein MS4A3 is negatively regulated by SATB1, and we found that MS4A3 expression was observed in primary acute myeloid leukemia cases. In addition , a MS4A3 antibody induced complement-dependent cell death in several human AML lines. These results suggest that MS4A3 may serve as a putative therapeutic target to treat myeloid malignancies.
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