2000 Fiscal Year Annual Research Report

造血幹細胞の発生と自己複製

Research Project

Project/Area Number	10181104
Research Institution	Kumamoto University
Principal Investigator	須田年生熊本大学, 発生医学研究センター, 教授 (60118453)
Co-Investigator(Kenkyū-buntansha)	帯刀益夫東北大学, 加齢医学研究所, 教授 (10099971) 中内啓光筑波大学, 基礎医学系, 教授 (40175485) 西川伸一京都大学, 医学研究科, 教授 (60127115) 溝口秀昭東京女子医科大学, 教授 (70049021) 中畑龍俊京都大学, 医学研究科, 教授 (20110744)
Keywords	AGM細胞 / Hemangioblast / VEカドヘリン / AML-1- / -マウス / 血管新生因子 / 骨髄移植療法 / ヒト細胞移植系 / ヒト造血幹細胞アッセイ系
Research Abstract	1)二次造血の開始期にみられる血管内造血における分子機構、および血液細胞と血管内皮細胞の相互作用について解析を進めた。二次造血が発生するAGM細胞を単離して、ストロマ細胞の上で共培養する系を確立し、血液細胞・血管内皮細胞の分化を試験管内で観察することが可能になった。最終的には、一個のHemangioblastから、血液細胞と同時に血管内皮細胞の分化誘導をはかり、造血細胞の分化決定の機構を探索する。VEカドヘリンやGATA-2転写因子の発現をGFPノックインしたES細胞の分化過程を追跡し、造血細胞および血管内皮細胞への分化に関与する分子の同定を開始した。 2)転写因子AML1の遺伝子破壊(AML-1-/-)マウスを用いて、また、造血幹細胞が血管新生を誘導するという、新しい幹細胞機能を提唱した。すなわち、幹細胞からAng-1などの血管新生因子が特異的に産生されていることが分かった。これは、閉塞性動脈疾患に対する骨髄移植療法に理論的根拠を与えるものとして注目される。 3)高度に純化されたマウス骨髄中の造血幹細胞を用いて、造血幹細胞のin vivoでの自己複製をクローナルに解析した。その結果、骨髄再構築能を有する造血幹細胞の細胞表面抗原は加齢によって変化することを明らかにした。 4)Common γ receptor KOマウスとNOD-SCIDマウスとを交配して、重症免疫不全マウスを作成し、高率なヒト細胞移植系を確立した。これにより、ヒト造血幹細胞のアッセイ系が確立したと考えられる。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Takakura N: "A role for hematopoietic cells in promoting angiogenesis."Cell. 102. 199-209 (2000)
[Publications] Ohneda O: "WECHE : a novel hematopoietic regulatory factor."Immunity. 12. 141-150 (2000)
[Publications] Yamashita J: "Embryonic stem cell derived Flk1-positive cells serve as vascular progenitors."Nature. 408. 92-96 (2000)
[Publications] Suda T: "Hematopoiesis and angiogeneis."Int J Hemat. 71. 99-107 (2000)
[Publications] Yanai N: "Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers."Blood. 96. 139-144 (2000)
[Publications] Ueda Y: "Expansion of human NOD/SCID-repopulating cells by a combination of stem cell factor, Flk2/Flt3 ligand, thrombopoietin and a complex of interleukin-6 and soluble interleukin-6 receptor."J Clin Invest. 105. 1013-1021 (2000)
[Publications] Suzuki A: "Flow-Cytometric Separation and Enrichment of Hepatic Progenitor Cells in the Developing Mouse Liver."Hepatology. 32. 1230-1239 (2000)
[Publications] Hsu HC: "Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver."Blood. 96. 3757-3762 (2000)
[Publications] Sudo K: "Age-associated characteristics of murine hematopoietic stem cells."J Exp Med. 192. 1273-1280
[Publications] Ema H: "In Vitro Self-Renewal Division of Hematopoietic Stem Cells."J Exp Med. 192. 1281-1288 (2000)
[Publications] Ema H: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo."Blood. 95. 2284-2288 (2000)
[Publications] Kubo H: "Vascular Endothelial Growth Factor Receptor-3 is essential for maintenance of integrity of endothelial cell lining during tumor angiogenesis,"Blood. 96. 546-553 (2000)
[Publications] Sato T: "Erythroid progenitors differentiate and mature in response to endogenous erythropoietin."J Clin Invest. 106. 263-270 (2000)
[Publications] Hamada k: "VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculo-angiogenesis and hematopoiesis."Blood. 96. 3793-3800 (2000)
[Publications] Miyamoto T: "An adherent condition is required for formation of multinuclear osteoclasts in the presence of M-CSF and RANKL."Blood. 96. 4335-4343 (2000)
[Publications] Yamada Y: "Exogenous clustered neuropilin-1 enhances vasculogenesis and angiogenesis."Blood. (in press). (2001)
[Publications] Zhang X-Q: "Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2^+ endothelial cells."Blood. (in press). (2001)
[Publications] Honda K: "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis."J.Exp.Med. (in press). (2001)
[Publications] Nakahata T: "Cell Therapy Ex vivo expansion of human hematopoietic stem cells"Springer. 105-106 (2000)
[Publications] Nakauchi H: "Cell Therapy Isolation and Characterization of CD34-Low/Negative Mouse Hematopoietic Stem cells."Springer. 95-103 (2000)

2000 Fiscal Year Annual Research Report

造血幹細胞の発生と自己複製

Principal Investigator

須田 年生 熊本大学, 発生医学研究センター, 教授 (60118453)

Research Products

[Publications] Takakura N: "A role for hematopoietic cells in promoting angiogenesis."Cell. 102. 199-209 (2000)

[Publications] Ohneda O: "WECHE : a novel hematopoietic regulatory factor."Immunity. 12. 141-150 (2000)

[Publications] Yamashita J: "Embryonic stem cell derived Flk1-positive cells serve as vascular progenitors."Nature. 408. 92-96 (2000)

[Publications] Suda T: "Hematopoiesis and angiogeneis."Int J Hemat. 71. 99-107 (2000)

[Publications] Yanai N: "Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers."Blood. 96. 139-144 (2000)

[Publications] Ueda Y: "Expansion of human NOD/SCID-repopulating cells by a combination of stem cell factor, Flk2/Flt3 ligand, thrombopoietin and a complex of interleukin-6 and soluble interleukin-6 receptor."J Clin Invest. 105. 1013-1021 (2000)

[Publications] Suzuki A: "Flow-Cytometric Separation and Enrichment of Hepatic Progenitor Cells in the Developing Mouse Liver."Hepatology. 32. 1230-1239 (2000)

[Publications] Hsu HC: "Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver."Blood. 96. 3757-3762 (2000)

[Publications] Sudo K: "Age-associated characteristics of murine hematopoietic stem cells."J Exp Med. 192. 1273-1280

[Publications] Ema H: "In Vitro Self-Renewal Division of Hematopoietic Stem Cells."J Exp Med. 192. 1281-1288 (2000)

[Publications] Ema H: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo."Blood. 95. 2284-2288 (2000)

[Publications] Kubo H: "Vascular Endothelial Growth Factor Receptor-3 is essential for maintenance of integrity of endothelial cell lining during tumor angiogenesis,"Blood. 96. 546-553 (2000)

[Publications] Sato T: "Erythroid progenitors differentiate and mature in response to endogenous erythropoietin."J Clin Invest. 106. 263-270 (2000)

[Publications] Hamada k: "VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculo-angiogenesis and hematopoiesis."Blood. 96. 3793-3800 (2000)

[Publications] Miyamoto T: "An adherent condition is required for formation of multinuclear osteoclasts in the presence of M-CSF and RANKL."Blood. 96. 4335-4343 (2000)

[Publications] Yamada Y: "Exogenous clustered neuropilin-1 enhances vasculogenesis and angiogenesis."Blood. (in press). (2001)

[Publications] Zhang X-Q: "Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2^+ endothelial cells."Blood. (in press). (2001)

[Publications] Honda K: "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis."J.Exp.Med. (in press). (2001)

[Publications] Nakahata T: "Cell Therapy Ex vivo expansion of human hematopoietic stem cells"Springer. 105-106 (2000)

[Publications] Nakauchi H: "Cell Therapy Isolation and Characterization of CD34-Low/Negative Mouse Hematopoietic Stem cells."Springer. 95-103 (2000)

須田年生熊本大学, 発生医学研究センター, 教授 (60118453)