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2001 Fiscal Year Annual Research Report

造血細胞の遺伝子操作

Research Project

Project/Area Number 10181105
Research InstitutionJichi Medical University

Principal Investigator

小澤 敬也  自治医科大学, 医学部, 教授 (30137707)

Co-Investigator(Kenkyū-buntansha) 吉田 進昭  東京大学, 医科学研究科, 教授 (10250341)
北村 俊雄  東京大学, 医科学研究科, 教授 (20282527)
谷 憲三朗  九州大学, 生体防御医学研究所, 教授 (00183864)
竹田 潤二  大阪大学, 医学部, 教授 (50163407)
生田 宏一  京都大学, 医学研究科, 助教授 (90193177)
Keywords遺伝子治療 / 造血幹細胞 / 選択的増幅遺伝子 / コモンマーモセット / レトロウイルスベクター / 突然変異マウス / サイトカインレセプター / トランスポゾンシステム
Research Abstract

体細胞あるいは生殖系列細胞の遺伝子操作を軸とした造血システムの研究を行った。
[造血幹細胞の直接的遺伝子操作] 1. 遺伝子導入造血幹細胞の選択的増幅システムの開発(小澤):新しいタイプの選択的増幅遺伝子として、分子スイッチにエリスロポエチン受容体を用いるものを開発し、従来型より効率が良いことを確認した。 2. 小型霊長類造血幹細胞の特徴化と遺伝子導入(谷):抗コモンマーモセットCD34単クローン抗体をクローン化した。GFP発現HIV(VSV)シュードタイプレンチウィルスベクターを用いて、コモンマーモセットCD34陽性細胞に遺伝子導入し、NOD/SCIDマウスへの移植実験を行った。 3. 幹細胞への効率の良い遺伝子導入法の開発(北村):ネコ内因性レトロウイルスRD114のenvを利用した新しいパッケイジング細胞PLAT-Fを樹立した。この系で作製したウイルスベクターで臍帯血由来造血細胞に遺伝子導入し、NOD/SCIDマウスへの移植実験を行った。
[発生工学的アプローチによる造血システムの解析] 1. 発生工学的手法を用いた造血・血管系システムの解析(吉田):リンパ浮腫を呈する突然変異マウスにおける血管からリンパ管への血流の移行に関して、小腸粘膜絨毛の毛細血管から中心リンパ管への移行に端を発している可能性が高いことが判明した。 2. IL-7Rのリンパ球増殖・分化シグナル(生田):IL-7レセプターのシグナル伝達分子のSTAT5が5'Jg1プロモーター領域に転写共役因子をリクルートし、ヒストンのアセチル化を介してTCRγ遺伝子座のクロマチン構造変換を促し、転写とDNA組換えを誘導することを示した。 3. マウストランスポゾンシステムを利用した造血系新規遺伝子の探索(竹田):個体内で効率よく移動するマウストランスポゾンを利用して網羅的遺伝子機能解析システムの樹立を推進した。

  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Kirito, K.: "Identification of the human erythropoietin receptor region required for Stat1 and Stat3 activation"Blood. (in press).

  • [Publications] Kirito, K.: "Constitutive activation of Stat1 and Stat3 in primary erythroleukemia cells"Int.J.Hematol.. (in press).

  • [Publications] Kirito, K.: "TPO regulates Bcl-xL gene expression through Stat5 and phosphatidylinositol-3-kinase activation pathways"J.Biol.Chem.. (in press).

  • [Publications] Kishino, K.: "Evaluation of engraftment by ABO genotypic analysis of erythroid burst-forming units after bone marrow transplantation"Leuk.Res.. 26. 13-17 (2002)

  • [Publications] Ohtsuki, T.: "Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex"Hum.Mol.Genet.. 10. 2651-2660 (2001)

  • [Publications] Yamashita, Y.: "Sak serine/threonine kinase acts as an effector of Tec tyrosine kinase"J.Biol.Chem.. 276. 39012-39020 (2001)

  • [Publications] Muramatsu, M.: "Reversible integration of the dominant negative retinoid receptor gene for ex vivo expansion of hematopoietic stem/progenitor cells"Biochem.Biophys.Res.Commun.. 27. 891-896 (2001)

  • [Publications] Miyazato, A.: "Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction"Blood. 98. 422-427 (2001)

  • [Publications] Kogure, K.: "Targeted integration of foreign DNA into a defined locus on chromosome 19 in K562 cells using AAV-derived components"Int.J.Hematol.. 73. 469-475 (2001)

  • [Publications] Mori, M.: "Antitumor effect of beta2-microglobulin in leukemic cell-bearing mice via apoptosis-inducing activity : activation of caspase-3 and nuclear factor-kappaB"Cancer Res.. 61. 4414-4417 (2001)

  • [Publications] Tanaka, M.: "Forkhead family transcription factor FKHRL1 is expressed in human megakaryocytes and regulates cell cycling as a downstream molecule of TPO signaling"J.Biol.Chem.. 276. 15082-15089 (2001)

  • [Publications] Hanazono, Y.: "Gene transfer into nonhuman primate hematopoietic stem cells : implications for gene therapy"Stem Cells. 19. 12-23 (2001)

  • [Publications] Uchida, M.: "A functional role of mitogen-activated protein kinases, Erk1 and Erk2, in the differentiation of a human leukemia cell line, UT-7/GM : A possible key factor for cell fate determination toward erythroid and megakaryocytic lineages"Int.J.Hematol.. 73. 78-83 (2001)

  • [Publications] Shinjyo, T.: "Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors"Mol.Cell.Biol.. 21. 854-864 (2001)

  • [Publications] Tabata, M.: "Stimulation of GATA-2 as a mechanism of hydrogen peroxide suppression in hypoxia-induced erythropoietin gene expression"J.Cell.Physiol.. 186. 260-267 (2001)

  • [Publications] Ooi, J.: "Unrelated cord blood translplantation for adult patients with MDS-related secondary acute myeloid leukaemia"Br.J.Haematol.. (in press).

  • [Publications] Ooi, J.: "Successful unrelated cord blood transplantation for relapse after autologous transplantation in non-Hodgkin's lymphoma"Leuk.Lymphoma. (in press).

  • [Publications] Tomonari, A.: "Severe autoimmune thrombocytopenia after allogeneic bone marrow transplantation for aplastic anemia"Int.J.Hematol.. (in press).

  • [Publications] Duda, D.G.: "Overexpression of the p53-induced brain angiogenesis inhibitor 1 suppresses efficiently tumor angiogenesis"Br.J.Cancer. (in press).

  • [Publications] Nagayama, H.: "Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim"Bone Marrow Transplant.. (in press).

  • [Publications] Kawai, K.: "Clinical course of an advanced renal cell carcinoma patient treated with GM-CSF gene therapy(GVAX) : The first experience of cancer gene therapy in Japan"Int.J.Urol.. (in press).

  • [Publications] Ohata, J.: "Differential graft-versus-leukemia effect by CD28 and CD40 costimulatory blockade after graft versus-host disease prophylaxis"Clin.Exp.Immunol.. (in press).

  • [Publications] Hibino, H.: "Haematopoietic progenitor cells from common marmoset as targets of gene transduction by retroviral and adenoviral vectors"Eur.J.Haematol.. 66. 272-280 (2001)

  • [Publications] Inazawa, T.: "Glucorticoid-regulated expression of exogenous human growth hormone gene in rats"Mol.Ther.. 4. 267-272 (2001)

  • [Publications] Kuwabara, T.: "Allosterically controllable maxizyme-mediated suppression of progression of leukemia in mice"Biomacromolecules. 2. 1220-1228 (2001)

  • [Publications] Ooi, J.: "Successful allogeneic bone marrow transplantation for hepatosplenic γδ T cell lymphoma"Hematologica. 86. E25 (2001)

  • [Publications] Tulin, E.E.: "Inhibition of human endothelial cell proliferation by ShIF, a vacuolar H+-ATPAse-like protein"Oncogene. (in press).

  • [Publications] Nosaka, T.: "Pim-1 expression is sufficient to induce cytokine independence in murin hematopoietic cells, but is dispensable for BCR-ABL-mediated transformation"Exp.Hematol.. (in press).

  • [Publications] Nakamura, T.: "Cytokine receptor common b subunit-mediated STAT5 activation confers NFkB activation through IkB-independent mechanism in a murine pro B cell line Ba/F3"J.Biol.Chem.. (in press).

  • [Publications] Kitamura, T.: "Role of MgcRacGAP/CYK4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation"Cell Structure and Function. (in press).

  • [Publications] Kagami, S.: "Role of stat5a in T helper cell differentiation"Blood. 97. 2358-2365 (2001)

  • [Publications] Hirose, K.: "MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody"J.Biol.Chem.. 276. 5821-5828 (2001)

  • [Publications] Kamizono, S.: "The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2"J.Biol.Chem.. 276. 12530-12538 (2001)

  • [Publications] Kawashima, T.: "STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-kB p65"J.Immunol.. 167. 3652-3660 (2001)

  • [Publications] Tonozuka, Y.: "Molecular cloning of a human novel type I cytokine receptor related to Delta1"Cytogenet.Cell Genet.. 93. 23-25 (2001)

  • [Publications] Ishido, M.: "Cholesterol requirement for receptor transport from multivesicular late endosomes to the Golgi"J.Cell Science. 114. 1965-1976 (2001)

  • [Publications] Tulin, E.E.: "A novel secreted form of immune suppressor factor with high homology to vacuolar ATPase identified by forward genetic approach of functional screening based on cell proliferation"J.Biol.Chem.. 276. 27519-27526 (2001)

  • [Publications] Kimura, M.: "Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group gene"Immunity. 15. 275-287 (2001)

  • [Publications] Senga, T.: "JAK/Stat3 dependent activation of RalGDS/Ral pathway in M1 mouse myeloid leukemic cells"J.Biol.Chem.. 276. 32678-32681 (2001)

  • [Publications] Frasor, J.: "Differential roles for Stat5a and Stat5b in prolactin stimulation of estrogen receptor a and b transcription"Mol.Endcrinol.. 15. 2172-2181 (2001)

  • [Publications] Yamamoto, S.: "Proleferation of parenchymal neural progenitors in response to injury in the adult rat spinal cord"Exp.Neurol.. 172. 115-127 (2001)

  • [Publications] Tokoro, Y.: "Molecular cloning and characterization of mouse tspan-3, a novel member of the tetraspanin superfamily, expressed on resting dendritic cells"Biochem.Biophys.Res.Commun.. 288. 178-183 (2001)

  • [Publications] Ueno, M.: "Identification of an embryonic dorsal aorta specific gene, endomucin, and its inhibitory activity on cell adhesion"Biochem.Biophys.Res.Commun.. 287. 501-506 (2001)

  • [Publications] Yamamoto, S.: "Transcription factor expression and Notch-dependent regulation of neural progenitors in the adult rat spinal cord"J.Neurosci.. 21. 9814-9823 (2001)

  • [Publications] Tulin, E.E.: "SF20, a novel bone marrow stroma-derived factor that binds to mouse TSA-1 and supports lymphoid cell proliferation"J.Immunol.. 167. 6338-6347 (2001)

  • [Publications] Arakawa, M.: "Negamycin can restore dystrophin in mdx sskeletal muscle"Acta Myologica. 20. 154-158 (2001)

  • [Publications] Tulin, E.E.: "Genetic approach and phenotype-based complementation screening for identification of stromal cell-derived proteins involved in cell proliferation"Exp.Cell Res.. 272. 23-31 (2002)

  • [Publications] Perez, O.D.: "Acitivation of the PKB/AKT pathway by ICAM-2"Immunity. 16. 51-65 (2002)

  • [Publications] Honke, K.: "Paranodal junction formation and spermatogenesis require sulfoglycolipids"Proc.Natl.Acad.Sci.USA. (in press).

  • [Publications] Ohtsuka, S.: "SH2-B is Required for both Male and Female Reproduction"Mol.Cell.Biol.. (in press).

  • [Publications] Fukuyama, H.: "Requirement of Fas expression in B cells for tolerance induction"Eur.J.Immunol.. 32. 223-230 (2002)

  • [Publications] Fukami, K.: "Requirement of phosholipase Cd4 for the first step of fertilization"Science. 292. 920-923 (2001)

  • [Publications] Hirata, A.: "Abnormalities of Synapses and Neurons in the Hippocampus of Neuropsin-Deficient Mice"Mol.Cell.Neurosci.. 17. 600-610 (2001)

  • [Publications] Lee, H.-C.: "Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice"Immunol.Lett.. (in press).

  • [Publications] Honda, K.: "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis"J.Exp.Med.. 193. 621-630 (2001)

  • [Publications] Agata, Y.: "Histone acetylation determines the developmentally regulated accessibility for T cell receptor-γ gene recombination"J.Exp.Med.. 193. 873-879 (2001)

  • [Publications] Lee, H.-C.: "Induction of germline transcription in the human T cell receptor γ locus by STAT5"J.Immunol.. 167. 320-326 (2001)

  • [Publications] Ohba, Y.: "Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis"EMBO J.. 20. 3333-3341 (2001)

  • [Publications] Ye, S.-K.: "Differential roles of cytokine receptors in the development of epidermal γ δ T cells"J.Immunol.. 167. 1929-1934 (2001)

  • [Publications] Fagarasan, S.: "In situ class switching and differentiation to IgA-producing cells in the gut lamina propria"Nature. 413. 639-643 (2001)

  • [Publications] Ye, S.-K.: "The IL-7 receptor controls the accessibility of the TCRγ locus by Stat5 and histone acetylation"Immunity. 15. 813-823 (2001)

  • [Publications] Nishimura, J.: "Efficient retrovirus-mediated PIG-A gene transfer and stable restoration of GPI-anchored protein expression in cells with the PNH phenotype"Blood. 97. 3004-3010 (2001)

  • [Publications] Kawane, K.: "Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver"Science. 292. 1546-1549 (2001)

  • [Publications] Horie, K.: "Efficient chromosomal transposition of a Tc1/mariner-like transposon Sleeping Beauty in mice"Proc.Natl.Acad.Sci.USA. 98. 9191-9196 (2001)

  • [Publications] Sano, S.: "Stat3 in thymic epithelial cells is essential for postnatal maintainance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)

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Published: 2003-04-03   Modified: 2016-04-21  

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