1998 Fiscal Year Final Research Report Summary
Mechanism of platelet production
Project/Area Number |
09480200
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cell biology
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Research Institution | The Institute of Physical and Chemical Research |
Principal Investigator |
TODOKORO Kazuo RIKEN,Molecular Cell Science Lab, Scientist, 分子細胞生物学研究室, 副主任研究員 (80172170)
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Co-Investigator(Kenkyū-buntansha) |
KOTANI Shuji RIKEN,Molecular Cell Science Lab, Postdoc.Scientist, 分子細胞生物学研究室, 基礎科学特別研究員 (60281622)
NAGATA Yuka RIKEN,Molecular Cell Science Lab, Postdoc.Scientist, 分子細胞生物学研究室, 基礎科学特別研究員 (40281620)
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Project Period (FY) |
1997 – 1998
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Keywords | Megakaryocytes / Platelets |
Research Abstract |
Molecular mechanism of platelet production still remains unclear. Therefore, we investigated the mechanism of megakaryocyte maturation processes, thrombopoietin (Tpo)-induced polyploidization of megakaryocytes, proplatelet formation of matured megakaryocytes, and Tpo-induced differentiation signal transduction. It has been described that polyploidization of megakaryocytes is due to DNA replication without mitosis, but we found that Tpo-induced primary megakaryocytes from bone marrows undergo polyploidization through unusual mitotic process. Mekagaryocytes go into mitosis until anaphase A, but at this stage the sister chromatids Would not go far apart enough to be separated nuclei. As for proplatelet formation, we found a factor in thrombocytopenic patients which stimulates proplatelet formation of mouse primary megakaryocytes in vitro. We are trying to isolate this factor by various chromatographic techniques. We also found that proplatelets were not produced from the megakaryocytes of NFE-2 knock-out mice. Thus we attempted to isolate a factor which is not expressed in NFE-2 knock-out mice, and a number of interesting factors were isolated. We are investigating the biological functions of these new factors.
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Research Products
(26 results)
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[Publications] Nagata, Y., Shozaki, Y., Nagahisa, H., Nagasawa, T., Abe, T.& Todokoro, K.: "Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis." Thromb.Haemost.77. 808-814 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Reese, TT., Gregory, RC., Sharlow, ER., Pacifici, R., Crouse, J.A., Todokoro, K.& Wojchowski, DM: "Epo-induced hemoglobinization of SKT6 cells is mediated by minimal cytoplasmic domains of the Epo or prolactin receptors without modulation of GATA-1 or EKLF." Growth Factors. 14. 161-176 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sharlow, ER., Pacifici, R., Crouse, J., Batac, J., Todokoro, K.& Wojchowski, DM.: "Hematopoietic cell phosphatase negatively regulates Epo-induced homoglobinization in erythroleukemic SKT6 cells." Blood. 90. 2175-2187 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Hamazaki, Y., Kojima, H., Mano, H., Nagata, Y., Todokoro, K., Abe, T.& Nagasawa, T.: "Tec is involved in G protein-coupled receptor-and integrin-mediated signalings in human blood platelets." Oncogene. 16. 2773-2779 (1998)
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[Publications] Kotani, S., Tugendreich, S., Fujii, M., Jorgensen, P-M., Watanabe, N., Hoog, C., Hieter, P.& Todokoro, K.: "PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression." Molecular Cell. 1. 371-380 (1998)
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[Publications] Gregory, R.C., Jiang, N., Todokoro, K., Crouse, J., Pacifici, R.E.& Wojchowski, D.M.: "Erythropoietin receptor and STAT5-specific pathways promote SKT6 cell hemoglobinization." Blood. 92. 1104-1118 (1998)
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[Publications] Osada, M., Komeno, T., Todokoro, K., Takizawa, M., Kojima, H., Suzukawa, K., Ninomiya, H., Tsukasa, A.& Nagasawa, T.: "Immature megakaryocytes undergo apoptosis in the absence of thrombopoietin." Exp.Hematol.27. 131-138 (1999)
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「研究成果報告書概要(欧文)」より
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