1997 Fiscal Year Annual Research Report

ヒト赤芽球系幹細胞の分化に伴うテロメア長とテロメラーゼ活性の推移

Research Project

Project/Area Number	08671204
Research Institution	HOKKAIDO UNIVERSITY
Principal Investigator	澤田賢一北海道大学, 医学部, 助教授 (90226069)
Keywords	CD34 / 純化法 / CD14 / テロメア長 / テロメレース / 脱核 / HTK / シグナル伝達
Research Abstract	ヒト赤芽球系幹細胞の分化に伴うテロメア長とテロメラーゼ活性の推移、およびその実験条件の設定に関する研究を行った結果、以下の点が明かとなり研究成果として報告、もしくは報告中である。1)実験系の確立のために、ヒト末梢血CD34陽性細胞の迅速・効率的、且つ経済的な純化法の開発を行った。純化前のCD14陽性細胞混入率と純化後のCD34陽性細胞純化率が逆相関することを科学的に証明し、CD14陽性細胞除去のためにナイロンファイバー・シリンジを開発し紹介した。さらに、本法を用いたヒト末梢血CD34陽性細胞の大量純化法を開発した。2)ヒトCD34陽性細胞の赤芽球への系特異的分化誘導法を確立し、その初期分化から最終分化(脱核)までの細胞表面抗原の変化、および増殖能の変化を検討した。その結果、チロシンキナーゼ受容体の一種であるHTKが赤芽球系前駆細胞に特異的に発現していること、ヒト赤芽球の脱核にはアクチンフィラメントが関与すること、エリトロポエチンによってJAK-STAT系のシグナル伝達が進行することを明らかにした。3)ヒト末梢血CD34陽性細胞の初期分化をより詳細に検討する目的で、赤芽球系のほか巨核球系への特異的分化誘導システムを開発し報告した。4)これまでの検討をもとにヒト末梢血CD34陽性細胞の赤芽球系特異的分化誘導を行い、赤芽球系前駆細胞の分化にともなうテロメア長の短縮とともに、興味ある現象としてBFU-Eレベルの前駆細胞におけるテロメラーゼ活性の一過性上昇を観察した。これは、細胞株には見られない現象であり、正常造血機構の解析の上で重要な知見であり、現在、継続してその差異の検討を行っている。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Oda,A.: "Erythropoietin induces tyrosine phosphorylation of Jak2,STAT5A and STAT5B in primary cultured human erythroid precursors." Blood. (in press).
[Publications] Koizumi,K.: "In vitro expansion of CD34+/CD41+ cells from human peripheral blood CD34+/CD41- cells : Role of cytokines for in vitro proliferation and differentiation of megakaryocytic progenitors." Experimental Hematol Hematology. (in press).
[Publications] Notoya,A.: "Subclinical alterations in coagulation and fibrinolysis in patients undergoing autologus peripheral blood stem cell transplantation." Leukemia & Lymphoma. (in press).
[Publications] Sawada,K.: "Growth characteristics of myelodysplastic CD34+cells." Leukemia and Lymphoma. (in press).
[Publications] Yamada,H.: "Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia." Seminars in Thrombosis and Hemostasis. (in press).
[Publications] Inada,T.: "Selective expression of the receptor tyrosine kinase,HTK,on human erythroid progenitor cells." Blood. 89. 2757-2765 (1997)
[Publications] Kumagai,K.: "Hepatitis B virus carriers in the treatment of malignant lymphoma : An epidemiological study in Japan." Annals of Oncology. 8. S109-S107 (1997)
[Publications] Yasukouchi,T.: "Roles of α 2-macroglobulin and its receptor in the regulation of the plasminogen-plasmin system." Jpn J Thrombosis Hemostasis. 8. 459-483 (1997)
[Publications] Koizumi,K.: "Effective high-dose chemotherapy followed by autologous peripheral blood sten cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis." Bome Marrow Transplantation. 20. 171-173 (1997)
[Publications] Yamaguchi,M.: "A rapid nylon-fiber syringe system to deplete CD14+ cells for positive selection of human blood CD34+ cells. Use of immunomagnetic microspheres." Bone Marrow. Transplantation. 19. 373-379 (1997)
[Publications] Ieko,M.: "Protection by α 2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1." British Journal of Haematology. 97. 214-218 (1997)
[Publications] Sawada,K.: "Role of cytokines in leukemic type growth of myelodysplastic CD34+ cells."
[Publications] Sawada,K.: "In vitro expansion of human peripheral blood CD34+ cells and transitional changes of proliferative capacity,in Sekiguchi,S (ed): Transfusion and Hematopoietic Stem Cells" Blackwell Scientific Publication Ltd., 21 (1996)

1997 Fiscal Year Annual Research Report

ヒト赤芽球系幹細胞の分化に伴うテロメア長とテロメラーゼ活性の推移

Principal Investigator

澤田 賢一 北海道大学, 医学部, 助教授 (90226069)

Research Products

[Publications] Oda,A.: "Erythropoietin induces tyrosine phosphorylation of Jak2,STAT5A and STAT5B in primary cultured human erythroid precursors." Blood. (in press).

[Publications] Koizumi,K.: "In vitro expansion of CD34+/CD41+ cells from human peripheral blood CD34+/CD41- cells : Role of cytokines for in vitro proliferation and differentiation of megakaryocytic progenitors." Experimental Hematol Hematology. (in press).

[Publications] Notoya,A.: "Subclinical alterations in coagulation and fibrinolysis in patients undergoing autologus peripheral blood stem cell transplantation." Leukemia & Lymphoma. (in press).

[Publications] Sawada,K.: "Growth characteristics of myelodysplastic CD34+cells." Leukemia and Lymphoma. (in press).

[Publications] Yamada,H.: "Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia." Seminars in Thrombosis and Hemostasis. (in press).

[Publications] Inada,T.: "Selective expression of the receptor tyrosine kinase,HTK,on human erythroid progenitor cells." Blood. 89. 2757-2765 (1997)

[Publications] Kumagai,K.: "Hepatitis B virus carriers in the treatment of malignant lymphoma : An epidemiological study in Japan." Annals of Oncology. 8. S109-S107 (1997)

[Publications] Yasukouchi,T.: "Roles of α 2-macroglobulin and its receptor in the regulation of the plasminogen-plasmin system." Jpn J Thrombosis Hemostasis. 8. 459-483 (1997)

[Publications] Koizumi,K.: "Effective high-dose chemotherapy followed by autologous peripheral blood sten cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis." Bome Marrow Transplantation. 20. 171-173 (1997)

[Publications] Yamaguchi,M.: "A rapid nylon-fiber syringe system to deplete CD14+ cells for positive selection of human blood CD34+ cells. Use of immunomagnetic microspheres." Bone Marrow. Transplantation. 19. 373-379 (1997)

[Publications] Ieko,M.: "Protection by α 2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1." British Journal of Haematology. 97. 214-218 (1997)

[Publications] Sawada,K.: "Role of cytokines in leukemic type growth of myelodysplastic CD34+ cells."

[Publications] Sawada,K.: "In vitro expansion of human peripheral blood CD34+ cells and transitional changes of proliferative capacity,in Sekiguchi,S (ed): Transfusion and Hematopoietic Stem Cells" Blackwell Scientific Publication Ltd., 21 (1996)

澤田賢一北海道大学, 医学部, 助教授 (90226069)