Hematopoietic stem ell support through transcriptional coactivator TRAP220
| Project/Area Number |
18591061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kobe University |
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Principal Investigator |
ITO Mitsuhiro Kobe University, School of Medicine, Professor (50362794)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Transcription Mediator / MED1 / TRAP220 / Knockout mice / Mouse embryonic fibroblasts / Hematopoieticstem / prosenitor cells / Cell growth / Apoptosis / 転写メディエーター / 造血支持細胞 / 核内受容体 / メディエーター / TRAP複合体 / 造血前駆細胞 |
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| Research Abstract |
TRAP/Mediator complex is a multiprotein coactivator complex that mediates the signals of a variety of activators. The TRAP220/MED1 subunit is known to act as a coactivator for ligand-dependent nuclear receptor signals and some other activators such as the GATA family proteins. We have recently shown that TRAP220 plays a key role in mediating signals of nuclear receptor-dependent differentiation of not only adipocytes but white blood cells (granulocytes and monocytes). Bone marrow hematopoiesis is achieved by both hematopoietic cells and niche cells, the latter of which are comprised of osteoblasts and other type(s) of mesenchymal cells. In this study we have evaluated the role of TRAP220 in niche cells.
Although the TRAP220 knockout mice am lethal before definitive hematopoiesis is dominant, the knockout mouse embryonic fibroblasts (MEF) are successfully prepared. Therefore, the MEFs, known to support hematopoietic stem/progenitor cells (HSPCs)in vitro, are used to check the ability to
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support the HSPCs. Indeed, the colony formation within the methylcellulose media was prominently decreased for bone marrow cells cultured for 6 to 8 weeks on mitomycin C-treated knockout MEFs, compared to those cultured on control MEFs. This result apparently demonstrates the role of TRAP220 in niche cells, which induce signals that mediate long-term support of HSPCs.
In order to see the short-term role of TRAP220 in MEF to support bone marrow cells, we then evaluated growth and survival of bone marrow cells cultured on knockout and control MEFs. The counts of bone marrow cells on knockout MEFs were significantly decreased compared to the control ever after the 2-days culture. To know the mechanism of decreased cell numbers, we analyzed DNA synthesis and apoptosis of bone marrow cells cultured on MEFs for one or two weeks. The incorporation of BrdU into bone marrow cells cultured on knockout MEFs was prominently decreased compared to the control. Furthermore, the apoptotic cells on knockout MEFs were less than those on the control. These results indicate that the MEFs secret the signal molecules that induce proliferation stress in bone marrow cells that eventually causes apoptosis simultaneously.
Thus, the TRAP220 in niche cells might mediate the signals both of the HSPCs support and the growth stress in hematopoietic progenitors. This is the first finding that the basic transctiptional coactivator complex might play a role in the hematopoietic niche. Less
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Alternative mechanisms by which Mediator subunit MEDI /TRA P220 regulates peroxisome prolifcrtor-activated receptor ganuna-stimulated adipogenesis and target gene expression2008
Author(s)
K, Ge., Y.-W, Cho., H, Quo., M. T, Hong., Guermah., M, Ito., H, Yu., M, Kalkm., R. G, Roeder
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Journal Title
Mol. Cell. Riol 28(3)
Pages: 1081-1091
Description
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[Journal Article] A kinase subunit of the human Mediator complex. CDKB. positively regulates transcriptional activation2007
Author(s)
T, Furumoto., A, Tanaka., M, Ito., S, Malik., Y, Hirose., B, Hanaoka., Y, Ohkuma
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Journal Title
Genes Cells 12(1)
Pages: 119-132
Description
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[Journal Article] Deregulation of a possible tumour suppressor gene, Z(23 H 120, by translocmion of RI K@ in transformed follicular lymphoma with t(2;6)(p 12:q25)2007
Author(s)
K, Minagawa., K, Yamamoto., S, Nishikawa., M, Ito., A, Sada., K, Yakushijin., A, Okamura., M, Shimoyama., Y, Katayama., T, Matsui
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Journal Title
Br. J. Haematal 139(1)
Pages: 161-163
Description
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[Presentation] Expression of pmteinase inhibitor 9(P1-9)and cytotoxic molecule granzyme B in leukocytes afterdlogcncie hematopoietic stem cell transplantation2007
Author(s)
O, Horie., T, Murayama., K, Saigo., K,Inoac., R, Ryo., M, Ito
Organizer
20th International Symposium on Technolugicd Innovations in Laboratory Hematology. Miami
Place of Presentation
FL, USA
Description
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[Presentation] Hcntatopoienc stem/progenitor cell support tlu'ounh transcriptional cnactivator TRA P2202007
Author(s)
M, Ito., K, Inoue., C, Iwasaki., N, Hasegawa., M, Morichika., A, Sada., N, Unthama., O, Flnrie
Organizer
69th Annual Meeting of Japanese Society of Hematology and 49th Annual Meeting of Japanese Society of Clinical Hematology
Place of Presentation
Yokohama
Description
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[Presentation] Expression of cytotoxic molecule granzyme B and its inhibitor P1-9 in lymphocytes after transplantation2007
Author(s)
O, Horie., T, Murayama., S, Toji., T, Minami., T, Tsuji., K, Inouc., K, Saigo., R, Ryo., M, Ito
Organizer
69th Annual Meeting of Japanese Society of Hematology and 490t Annual Meeting ofJapanese Society of Clinical Hematology
Place of Presentation
Yokohama
Description
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[Presentation] Growth of hematopoietic cells through transcriptional coactivator MEDI/FRAP220 in hematopoietic niche2007
Author(s)
K, Inoue., C, Iwasak.i, N, Hasegawa., M, Morichika., A, Sada., N, Urahama., O, Rorie., Itn
Organizer
30th Annual Meeting of Molecular Biology Society of Japan and 80th Annual Meeting of Japanese Society of Biochemistry
Place of Presentation
Yokohama
Description
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[Presentation] Ratio of expressions of cytotoxic molecule granzyme B and its intrinsic inhibitor PI-9 in lymphocytes2007
Author(s)
O, Horie., S, Toji., T, Murayama., T, Minami., T, Tsuji., K, Inoue., K, Saigo., R, Ryo., M, Ito
Organizer
30th Annual Meeting of Molecular Biology Society of Japan and 80th Annual Meeting of Japanese Society of Biochemistry
Place of Presentation
Yokohama
Description
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[Presentation] The role of proteinatac inhibitor 9(P1-9)in gnuzyme B/perforin-medimcd eytota.iei ty induced by cylutoxie T cells in allogeneie hematopoietic stem cell transfusion2006
Author(s)
O, Norio., T, Mursyama., K, Saigo., Y, Utsunomiya., R, Ryo., M, Ito
Organizer
48th Annual Meeting of the American Society of Hematology. Orlando. FL
Place of Presentation
USA
Description
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