Grant-in-Aid for Scientific Research (A)
|Research Institution||jichi Medical School|
MIURA Yasusada Jichi Medical School, Professor, 医学部, 教授 (60048965)
MUROI Kazuo Jichi Medical School, Assistant Professor, 医学部, 講師 (50190939)
清水 律子 自治医科大学, 医学部, 助手 (40226262)
IMAGAWA Shigehiko Jichi Medical School, Assistant Professor, 医学部, 講師 (60231164)
HATAKE Kiyohiko Jichi Medical School, Associate Professor, 医学部, 助教授 (80192699)
KOMATSU Norio Jichi Medical School, Assistant Professor, 医学部, 講師 (50186798)
TAKATOKU Masaaki Jichi Medical School, Assistant, 医学部, 助手 (20285787)
|Project Fiscal Year
1995 – 1997
Completed(Fiscal Year 1997)
|Budget Amount *help
¥33,800,000 (Direct Cost : ¥33,800,000)
Fiscal Year 1997 : ¥5,400,000 (Direct Cost : ¥5,400,000)
Fiscal Year 1996 : ¥7,700,000 (Direct Cost : ¥7,700,000)
Fiscal Year 1995 : ¥20,700,000 (Direct Cost : ¥20,700,000)
|Keywords||hemopoietic stem cell / hemopoietic factor / erythropoietin gene / megakaryocytic cell line / transcription factor / erythropoietin receptor / hemopoietic stem cell disorders / apoptosis / 造血幹細胞 / 造血因子 / 受容体 / シグナル伝達 / 巨核球株細胞 / 赤芽球分化 / STAT転写因子群 / アポトーシス / GATA-1 / 赤白血病|
Molecular control of the regulation of hemopoiesis and clinical application
1.We investigated molecular control of the regulation of hemopoiesis using a megakaryocytic cell line UT-7 and its sublines.
After culturing long time with GM-CSF,we established an immature blastic subline UT-7/GM.This cell line differentiates into erythroid lineage by the addition of erythropoietin (EPO), and into megakaryocytic lineage by thrombopoietin (TPO). GM-
CSF suppresses its differentiation. Transcription factors STAT 1alpha, 3 and 5 were activated by GM-CSF and TPO,while only STAT1alpha was activated by EPO.The detailed mechanism was investigated using transfetants of STAT molecules.
2.By the continuous addition of TPO,we established a TPO-dependent sub-cell line, which expresses megakaryocytic feature, and characterized its signal pathway following the addition of TPO.
3.We reported that regulation of EPO receptor gene is cycle dependent, by using UT-7 cell line.
4.Disialosyl-T antigen was found to be involved in the erythroid differentiation.
5.GATA sequence at 5'promotor region of EPO gene was found to suppress the expression of EPO gene
6.Role of apoptosis-related genes, Fas bcl-x etc was investigated.
7.7.We could not find any mutation in a patient with congenital megakaryopenic thrombocytopenia. In this concern, primitive cd34+stem cells express TPO receptor K.After differentiation by culturing with TPO,they express P type receptors. This may shed a light on the role of K type receptor.