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ES細胞を用いた霊長類ヘマンジオブラストの同定とその増殖・分化機構の解明

Research Project

Project/Area Number 17014052
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University

Principal Investigator

中畑 龍俊  京都大学, 医学研究科, 教授 (20110744)

Co-Investigator(Kenkyū-buntansha) 足立 壮一  京都大学, 医学研究科, 講師 (10273450)
梅田 雄嗣  京都大学, 医学研究科, 助手 (80397538)
Project Period (FY) 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 2005: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsES細胞 / ヘマンギオブラスト / 霊長類 / ヒト / 造血幹細胞 / 血管内皮細胞 / がん進展 / 分化
Research Abstract

腫瘍や白血病の進展に血管新生が大きく関わっている。マウスでは血管と血液細胞は同じ母細胞(ヘマンギオブラスト)から生まれてくるとする報告が相次いでいるが、霊長類ではヘマンギオブラストの存在は証明されていない。本研究では、サルES細胞を用いてその分化過程を詳細に検討することにより、ヘマンギオブラストの同定、血液細胞と血管内皮細胞への分化機構やその分子基盤を明らかにする事を目的としている。本研究の成果は血管内皮や造血幹細胞の発生や正常の増殖分化過程を明らかにするとともに、癌や白血病の進展と血管噺生の関係を明らかにする上で多くの情報を提供することであろう。本年度以下の成果が得られた。
(1)マウスES細胞から中胚葉細胞に分化させた後、FLK1+細胞を純化し培養すると血液、血管内皮、心筋が出現することから3者に共通の母細胞の存在が示唆された。現在、この過程で、マウスの造血機能を長期にわたって維持する造血幹細胞の形成の有無について、移植により検討を行っている。
(2)サルES細胞から胎児型の血液細胞と成体型の血液細胞の両者および血管内皮細胞を誘導することが可能となった。サルでもマウスと同様、血液と血管内皮の共通の母細胞であるヘマンギオブラストの存在が明らかとなった。
(3)ヒトES細胞を用いた研究を開始した。各種血液細胞、血管内皮細胞のシートを産生する事に成功した。ヒトヘマンギオブラストの同定、その増殖、分化機構について検討を始めた。
(4)ヒト体性幹細胞測定のためのNOD/SCID/γc-/-(NOG)マウスを開発した。このマウスにヒト造血幹細胞を移植するとマウス体内でTリンパ球を含むすべてのヒト型血球が長期にわたり産生されることが明らかとなった。この系を用いてヒトヘマンギオブラストのin vivoで分化機構について解析予定である。

Report

(1 results)
  • 2005 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 Other

All Journal Article (27 results)

  • [Journal Article] 幹細胞を用いた再生医長の進展2006

    • Author(s)
      中畑龍俊
    • Journal Title

      実験医学 24

      Pages: 108-113

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 小児の難治性貧血2006

    • Author(s)
      中畑龍俊
    • Journal Title

      実験医学 61

      Pages: 98-106

    • Related Report
      2005 Annual Research Report
  • [Journal Article] limited ability of antigen-specific Th1 responses to inhibit Th2 cell development in vivo.2005

    • Author(s)
      Yasumi T
    • Journal Title

      J.Immunol 177

      Pages: 1325-1331

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Early-onset sarcoidosis and CARD15 mutations : common genetic etiology with Blau syndrome.2005

    • Author(s)
      Kanazawa N
    • Journal Title

      Blood 105

      Pages: 1195-1197

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel NF-kB inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-kit receptors.2005

    • Author(s)
      Tanaka A
    • Journal Title

      Blood 105

      Pages: 2324-2331

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Stem cell factor has a suppressive activity to IgE-mediated chem. otaxis of mast cells.2005

    • Author(s)
      Sawada J
    • Journal Title

      J.Immunol. 174

      Pages: 3626-3632

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of leukemiac cell growth by a novel anti-cancer drug (GUT-70) from calophylim brasiilense that acts by induction of apoptosiss.2005

    • Author(s)
      Kimura S
    • Journal Title

      Int.J.Cancer 133

      Pages: 158-165

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CpG inhibits IgE clas switch recombination through suppression of NFkB activity, out not through Id2 or Bcl6. Biochem.2005

    • Author(s)
      Kusunoki, T
    • Journal Title

      Biophys.Res.Commun. 328

      Pages: 499-506

    • Related Report
      2005 Annual Research Report
  • [Journal Article] SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis.2005

    • Author(s)
      Kusunoki, T
    • Journal Title

      J.Allergy Clin.Immunol. 115

      Pages: 636-638

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characterization of mouse hepatic stem/progenytor cells in a novel culture system.2005

    • Author(s)
      Tsuchiya A
    • Journal Title

      Gastroenterology 128

      Pages: 2089-2104

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Two different role of purified Cd45+ hematopoietic stem cells after transplantation in muscles.2005

    • Author(s)
      Yoshimoto M
    • Journal Title

      Stem Cells 23

      Pages: 610-618

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prospective characterization of neural stem cells by flow cytometry analysis using combination of the surface markers.2005

    • Author(s)
      Nagato M
    • Journal Title

      J.Neurosci.Res. 80

      Pages: 456-466

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CD34+CD7+ leukemoc Progenitor cells may be involved in maintenance and clonal evolution of chronic myeloid leukemia.2005

    • Author(s)
      Kosugi N
    • Journal Title

      Clin.Cancer Res. 11

      Pages: 505-511

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Acetylation of GATA-4 is involved in the differentiation of embryonic stem cells into cardiac myocytes.2005

    • Author(s)
      Kawamura T
    • Journal Title

      J.Biol.Chem. 280

      Pages: 19682-19688

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Somatic mosaicism of CIAS1 in a patient with chronic infantile neurologic, cutaneous, articular syndrome.2005

    • Author(s)
      Saito M
    • Journal Title

      Arthritis & Rheumatism 52

      Pages: 3579-3585

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 造血系幹細胞2005

    • Author(s)
      中畑龍俊
    • Journal Title

      ティッシュエンジニアリング2005 1

      Pages: 11-17

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 造血幹細胞移植2005

    • Author(s)
      中畑龍俊
    • Journal Title

      予防医学事典

      Pages: 378-378

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 肥満細胞の分化機構と病態的役割2005

    • Author(s)
      神戸直智
    • Journal Title

      日本小児血液学会雑誌 19

      Pages: 113-122

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 小児急性リンパ性白血病に対する移植前全身照射法の実態2005

    • Author(s)
      鈴木信寛
    • Journal Title

      日本小児血液学会雑誌 19

      Pages: 131-136

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Therapy-related myelodysplastic syndrome in childhood : A retrospective study of 36 patients in Japan.

    • Author(s)
      Tsurusawa M
    • Journal Title

      Leukemia Res. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Methylation status of the p15 and p16 genes in paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia.

    • Author(s)
      Hasegawa D
    • Journal Title

      Brit.J.Haematol. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] HOX decoy peptide enhances the ex vivo expansion of human umbilical cord blood HSCs.

    • Author(s)
      Tanaka H
    • Journal Title

      Stem Cells (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] RAS-blocking bisphosphonate zoledronic acid inhibits the abnormal proliferation and differentiation of juvenile myelomonocytic leukemia cells.

    • Author(s)
      Ohtsuka Y
    • Journal Title

      Blood (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel variant fibrinogen, deletion of Bγ111Ser in coiled-coil region, affecting fibrin lateral aggregation.

    • Author(s)
      Okumura N
    • Journal Title

      Clinica Chimica ACTA (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Acute lymphoblastic leukemia with a germline MLL gene can be cured in a high proportion of infants with use of intensive chemotherapy : results from the Japan Infant Leukemia Study Group.

    • Author(s)
      Nagayama J
    • Journal Title

      Blood (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification and characterization of hemangioblasts during cynomolgus monkey embrionic stem cell differentiation.

    • Author(s)
      Umeda K
    • Journal Title

      Stem Cells (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A neurosphere-derived factor(NDF), Cystatin C, supports differentiation of ES cells into neural stem cells.

    • Author(s)
      Kato T
    • Journal Title

      Proc.Natl Acad.Sci.USA (in press)

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2018-03-28  

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