2003 Fiscal Year Annual Research Report

血管・血液システムの成立機構の解明と細胞治療を目指したES細胞の分化

Research Project

Project/Area Number	12219209
Research Institution	The Institute of Physical and Chemical Research
Principal Investigator	西川伸一独立行政法人理化学研究所, 幹細胞研究グループ, グループディレクター (60127115)
Co-Investigator(Kenkyū-buntansha)	植村明嘉独立行政法人理化学研究所, 幹細胞研究グループ, 研究員大沢匡毅独立行政法人理化学研究所, 幹細胞研究グループ, 研究員 (10344029) 江良択実独立行政法人理化学研究所, 幹細胞研究グループ, 研究員 (00273706) 戸川温独立行政法人理化学研究所, 幹細胞研究グループ, 研究員 (30359799)
Keywords	ES細胞 / 血管新生 / ガン周囲組織 / 血液細胞 / 抹消リンパ組織
Research Abstract	本年度は、目先の業績にこだわらず、幹細胞とニッチの相互作用に関わる分子についての遺伝子クローニング、ES細胞から様々な中胚葉系列の分化を選択的に誘導方の開発に焦点を絞り、方法や材料の開発も含めて長期的視点に立った研究を行った。実際、1、色素細胞を容易に選択できるマウスの開発、2、毛根調整法の開発、3、全く新しい単一細胞PCRライブラリー作成法の開発、4、ほぼ全ての中胚葉を分別できるES細胞株の開発、5、特定の中胚葉系列を選択的に誘導できる無血清培養条件の開発、など将来他の分野でも有用な様々な材料と方法の開発に成功した。本年の後半から、これら材料や方法を駆使した実際の実験に入っており、幹細胞とニッチについては、幹細胞特異的に発現している遺伝子を様々な方法で約50個まで絞り込んだ。同様に、ニッチ細胞特異的遺伝子も同じように絞込みが終わり、一部の興味ある遺伝子について機能解析を始めるとともに、更に絞込みをするための方法を考案し進めている。遺伝子ハンティングについては、論文にするまでまだ時間がかかると予想しているが、Bcl2の色素細胞における役割、幹細胞プロファイルなど新しい知見を得たので、これについては論文を書き始めたところである。一方、中胚葉分化については材料や方法の開発はほぼ終了し、1、これまで想像されていた内胚葉と中胚葉に分化するmesendoderm細胞の存在が確かに存在することの証明、2、未熟内胚葉幹細胞株の樹立、3、中胚葉初期分化段階での可塑性の証明、4、成体幹細胞の一部が神経堤由来であることの証明、5、胚外型、原条型、中内胚葉型、ノード型の4種類の中胚葉分化経路を証明し、それぞれを選択的に誘導する無血清条件の開発など、予想以上の成果を得始めており、これらは現在論文にまとめている段階である。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Fraser, S.T.et al.: "Putative intermediate precursor between hematogenic endothelial cells and blood cells in the developing embryo"Develop.Growth Differ.. 45・1. 63-75 (2003)
[Publications] Fraser, S.T.et al.: "In vitro differentiation of mouse embryonic stem cells : hematopoietic and vascular cell types"Methods Enzymol. 365. 59-72 (2003)
[Publications] Hidaka, K.et al.: "Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells"The FASEB Journal. 17・6. 740-742 (2003)
[Publications] Hirai, H.et al.: "Hemogenic and nonhemogenic endothelium can be distinguished by the activity of fetal liver kinase(Flk)-1 promoter/enhancer during mouse embryogenesis"Blood. 101・3. 886-893 (2003)
[Publications] Hirashima, M.et al.: "A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells"Blood. 101・6. 2261-2267 (2003)
[Publications] Hirobe, T.et al.: "Steel factor controls the proliferation and differentiation of neonatal mouse epidermal melanocytes in culture"Pigment Cell Res. 16・6. 644-655 (2003)
[Publications] Kunkel, D.et al.: "Visualization of peptide presentation following oral application of antigen in normal and Peyer's patches-deficient mice"Eur J Immunology. 33・5. 1292-1301 (2003)
[Publications] Matsumura, K.et al.: "Modulation of VEGFR-2-mediated endothelial-cell activity by VEGF-C/VEGFR-3"Blood. 101・4. 1367-1374 (2003)
[Publications] Minegishi, N.et al.: "Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos"Blood. 102・3. 896-905 (2003)
[Publications] Nakamura, Y.et al.: "Phospholipase Cdelta(1) is required for skin stem cell lineage commitment"Embo J. 22・12. 2981-2991 (2003)
[Publications] Nishikawa, S.et al.: "Organogenesis of peripheral lymphoid organs"Immunology reviews. 195. 72-80 (2003)
[Publications] Nishikawa, S.et al.: "Regenerative medicine and vascular biology"Ophthalmologica. 217・1. 19-27 (2003)
[Publications] Schroeder, T.et al.: "Recombination signal sequence-binding protein J{kappa}alters mesodermal cell fate decisions by suppressing cardiomyogenesis"Proc Natl Acad Sci USA. 100. 4018-4023 (2003)
[Publications] Sone, M.et al.: "Different Differentiation Kinetics of Vascular Progenitor Cells in Primate and Mouse Embryonic Stem Cells"Circulation. 107. 2085-2088 (2003)
[Publications] Takenaka, K.et al.: "Role of phospholipase C-L2, a novel phospholipase C-like protein that lacks lipase activity, in B-cell receptor signaling"Mol Cell Biol. 23・20. 7329-7338 (2003)
[Publications] Watabe, T.et al.: "TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells"J Cell Biol. 163・6. 1303-1311 (2003)
[Publications] Yamazaki, D.et al.: "WAVE2 is required for directed cell migration and cardiovascular development"Nature. 424・6947. 452-456 (2003)
[Publications] Yoshino, M.et al.: "Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption"Journal of Bone and Mineral Research. 18・1. 108-116 (2003)
[Publications] Yurugi-Kobayashi, T.et al.: "Effective contribution of transplanted vascular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage"Blood. 101・7. 2675-2678 (2003)
[Publications] Hirobe, T.et al.: "Hepatocyte Growth Factor Controls the Proliferation of Cultured Epidermal Melanoblasts and Melanocytes from Newborn Mice"Pigment Cell Res. 17・1. 51-61 (2004)
[Publications] Weston, J.A.et al.: "Neural crest and the origin of ectomesenchyme : Neural fold heterogeneity suggests an alternative hypothesis"Dev Dyn. 229・1. 118-130 (2004)

2003 Fiscal Year Annual Research Report

血管・血液システムの成立機構の解明と細胞治療を目指したES細胞の分化

Principal Investigator

西川 伸一 独立行政法人理化学研究所, 幹細胞研究グループ, グループディレクター (60127115)

Research Products

[Publications] Fraser, S.T.et al.: "Putative intermediate precursor between hematogenic endothelial cells and blood cells in the developing embryo"Develop.Growth Differ.. 45・1. 63-75 (2003)

[Publications] Fraser, S.T.et al.: "In vitro differentiation of mouse embryonic stem cells : hematopoietic and vascular cell types"Methods Enzymol. 365. 59-72 (2003)

[Publications] Hidaka, K.et al.: "Chamber-specific differentiation of Nkx2.5-positive cardiac precursor cells from murine embryonic stem cells"The FASEB Journal. 17・6. 740-742 (2003)

[Publications] Hirai, H.et al.: "Hemogenic and nonhemogenic endothelium can be distinguished by the activity of fetal liver kinase(Flk)-1 promoter/enhancer during mouse embryogenesis"Blood. 101・3. 886-893 (2003)

[Publications] Hirashima, M.et al.: "A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells"Blood. 101・6. 2261-2267 (2003)

[Publications] Hirobe, T.et al.: "Steel factor controls the proliferation and differentiation of neonatal mouse epidermal melanocytes in culture"Pigment Cell Res. 16・6. 644-655 (2003)

[Publications] Kunkel, D.et al.: "Visualization of peptide presentation following oral application of antigen in normal and Peyer's patches-deficient mice"Eur J Immunology. 33・5. 1292-1301 (2003)

[Publications] Matsumura, K.et al.: "Modulation of VEGFR-2-mediated endothelial-cell activity by VEGF-C/VEGFR-3"Blood. 101・4. 1367-1374 (2003)

[Publications] Minegishi, N.et al.: "Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos"Blood. 102・3. 896-905 (2003)

[Publications] Nakamura, Y.et al.: "Phospholipase Cdelta(1) is required for skin stem cell lineage commitment"Embo J. 22・12. 2981-2991 (2003)

[Publications] Nishikawa, S.et al.: "Organogenesis of peripheral lymphoid organs"Immunology reviews. 195. 72-80 (2003)

[Publications] Nishikawa, S.et al.: "Regenerative medicine and vascular biology"Ophthalmologica. 217・1. 19-27 (2003)

[Publications] Schroeder, T.et al.: "Recombination signal sequence-binding protein J{kappa}alters mesodermal cell fate decisions by suppressing cardiomyogenesis"Proc Natl Acad Sci USA. 100. 4018-4023 (2003)

[Publications] Sone, M.et al.: "Different Differentiation Kinetics of Vascular Progenitor Cells in Primate and Mouse Embryonic Stem Cells"Circulation. 107. 2085-2088 (2003)

[Publications] Takenaka, K.et al.: "Role of phospholipase C-L2, a novel phospholipase C-like protein that lacks lipase activity, in B-cell receptor signaling"Mol Cell Biol. 23・20. 7329-7338 (2003)

[Publications] Watabe, T.et al.: "TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells"J Cell Biol. 163・6. 1303-1311 (2003)

[Publications] Yamazaki, D.et al.: "WAVE2 is required for directed cell migration and cardiovascular development"Nature. 424・6947. 452-456 (2003)

[Publications] Yoshino, M.et al.: "Reduction of osteoclasts in a critical embryonic period is essential for inhibition of mouse tooth eruption"Journal of Bone and Mineral Research. 18・1. 108-116 (2003)

[Publications] Yurugi-Kobayashi, T.et al.: "Effective contribution of transplanted vascular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage"Blood. 101・7. 2675-2678 (2003)

[Publications] Hirobe, T.et al.: "Hepatocyte Growth Factor Controls the Proliferation of Cultured Epidermal Melanoblasts and Melanocytes from Newborn Mice"Pigment Cell Res. 17・1. 51-61 (2004)

[Publications] Weston, J.A.et al.: "Neural crest and the origin of ectomesenchyme : Neural fold heterogeneity suggests an alternative hypothesis"Dev Dyn. 229・1. 118-130 (2004)

西川伸一独立行政法人理化学研究所, 幹細胞研究グループ, グループディレクター (60127115)