Identification and functional analysis of molecules which regulate the earliest events in lymphopoiesis

• Project/Area Number: 19591110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: YOKOTA Takafumi Osaka University, 医学系研究科, 助教 (60403200)
• Co-Investigator(Kenkyū-buntansha): ORITANI Kenji 大阪大学, 医学系研究科, 講師 (70324762) ; KANAKURA Yuzuru 大阪大学, 医学系研究科, 教授 (20177489)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 血液免疫学 / リンパ球 / 造血幹細胞 / Wntシグナル / 妊娠 / エストロゲン / sFRP1

Research Abstract

妊娠および性ステロイドホルモンであるエストロジェンは、リンパ球分化の極めて初期の段階を抑制することを明らかにした。そのメカニズムとして、エストロジェンが骨髄造血環境を構築する間質細胞に作用し、Wntシグナルの調節分子として知られるsoluble Frizzled-relateprotein 1(sFRP1)の分泌を亢進させること、さらにはsFRP1が未分化な造血前駆細胞に作用してリンパ球への分化を抑制することを明らかにした。

Research Products

• [Journal Article] The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice (2009)
  • Author(s): Yokota T, Oritani K, Butz S, Kokame K, Kincade PW, Miyata T, Vestweber D, Kanakura Y
  • Journal Title: Blood 113 Pages: 2914-2923
  • Peer Reviewed
• [Journal Article] The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice. (2009)
  • Author(s): Yokota T, et al.
  • Journal Title: Blood in press
  • Peer Reviewed
• [Journal Article] Soluble Frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis (2008)
  • Author(s): Yokota T, Oritani K, Garrett KP, Kouro T, Nishida M, Takahashi I, Ichii M, Satoh Y, Kincade PW, Kanakura Y
  • Journal Title: The Journal of Immunology 181 Pages: 6061-6072
  • Peer Reviewed
• [Journal Article] Regulation of human B lymphopoiesis by the transforming growth factor-beta superfamily in a newly established coculture system using human mesenchymal stem cells as a supportive microenvironment (2008)
  • Author(s): Ichii M, Oritani K, Yokota T, Nishida M, Takahashi I, Shirogane T, Ezoe S, Saitoh N, Tanigawa R, Kincade PW, Kanakura Y.
  • Journal Title: Experimental Hematology 36 Pages: 587-597
  • Peer Reviewed
• [Journal Article] Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice (2008)
  • Author(s): Li W, Ishihara K, Yokota T, Nakagawa T, Koyama N, Jin J, Mizuno-Horikawa Y, Wang X, Miyoshi E, Taniguchi N, Kondo A
  • Journal Title: Glycobiology 18 Pages: 114-124
  • Peer Reviewed
• [Journal Article] Soluble Frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis. (2008)
  • Author(s): Yokota T, et al.
  • Journal Title: Journal of Immunology 181 Pages: 6061-6072
  • Peer Reviewed
• [Journal Article] Regulation of human B lymphopoiesis by the transforming growth factor-beta superfamily in a newly established coculture system using human mesenchymal stem cells as a supportive microenvironment. (2008)
  • Author(s): Ichii M, et al.
  • Journal Title: Experimental Hematology 36 Pages: 567-597
  • Peer Reviewed
• [Journal Article] Reduced [alpha] 4 [beta] 1 integrin/VCAM-1 interactions lead to impaired Pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice. (2008)
  • Author(s): Li W, et. al.
  • Journal Title: Glycobiology 18 Pages: 114-124
  • Peer Reviewed
• [Journal Article] Adiponectin binds to chemokines via the globular head and modulates interactions between chemokines and heparan sulfates. (2007)
  • Author(s): Masaie H, et. al.
  • Journal Title: Experimental Hematology 35 Pages: 947-956
  • Peer Reviewed
• [Presentation] The endothelial antigen ESAM marks hematopoietic stem cells throughout life in mice. (2008)
  • Author(s): 横田貴史
  • Organizer: アメリカ血液学会
  • Place of Presentation: 米国 サンフランシスコ
  • Year and Date: 2008-12-09
• [Presentation] 造血幹細胞とリンパ球初期分化 (2008)
  • Author(s): 横田貴史
  • Organizer: 第6回先端医療フォーラム
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-24
• [Presentation] 新規造血幹細胞表面マーカーESAM1の同定 (2008)
  • Author(s): 横田貴史
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-05-16
• [Presentation] The endothelial antigen ESAM marks hematopoietic stem cells throughout life in mice (2008)
  • Author(s): Yokota T, Oritani K, Butz S, Kokame K, Kincade PW, Miyata T, Vestweber D, Kanakura Y
  • Organizer: The American Society of Hematology 50th Annual meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] 新規造血幹細胞表面抗原の同定 (2008)
  • Author(s): 横田貴史
  • Organizer: 第14回血液科学セミナー
  • Place of Presentation: 東京
• [Presentation] 新規造血幹細胞表面マーカーESAM1の同定 (2008)
  • Author(s): 横田貴史、織谷健司、小亀浩市、宮田敏行、金倉 譲
  • Organizer: 第6回幹細胞シンポジウム
  • Place of Presentation: 東京
• [Presentation] SFRP1 is estrogen inducible in bone marrow stromal cells and suppresses the ear liest events in lymphopoiesis. (2007)
  • Author(s): 横田貴史
  • Organizer: アメリカ血液学会
  • Place of Presentation: 米国 アトランタ
  • Year and Date: 2007-12-10
• [Presentation] SFRP1 is estrogen inducible in bone marrow stromal cells and suppresses the ear liest events in lymphopoiesis. (2007)
  • Author(s): 横田貴史
  • Organizer: 日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-20
• [Presentation] Estrogenが誘導する骨髄間質細胞分泌蛋白sFRPlはリンパ球初期分化を負に制御する (2007)
  • Author(s): 横田貴史
  • Organizer: 日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-11
• [Presentation] SFRP1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis (2007)
  • Author(s): Yokota T, Oritani K, Garrett KP, Kouro T, Nishida M, Takahashi I, Ichii M, Matsumura I, Kincade PW, Kanakura Y.
  • Organizer: The American Society of Hematology 49th Annual meeting
  • Place of Presentation: Atlanta, USA
• [Presentation] 第37回日本免疫学会総会 (2007)
  • Author(s): Yokota T, Oritani K, Kouro T, Ichii M, Kincade PW, Kanakura Y
  • Organizer: SFRP1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis
• [Presentation] Estrogenが誘導する骨髄間質細胞分泌蛋白sFRP1 はリンパ球初期分化を負に制御する (2007)
  • Author(s): 横田貴史、織谷健司、Paul W. Kincade、高橋功、一井倫子、松村到、金倉譲
  • Organizer: 第69回日本血液学会総会
  • Place of Presentation: 横浜