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2004 Fiscal Year Annual Research Report

幹細胞の可塑性と未分化性維持機構

Research Project

Project/Area Number 14081101
Research InstitutionThe University of Tokyo

Principal Investigator

中内 啓光  東京大学, 医科学研究所, 教授 (40175485)

Co-Investigator(Kenkyū-buntansha) 丹羽 仁史  理化学研究所, 多能性幹細胞研究チーム, チームリーダー (80253730)
横田 崇  金沢大学, 医学系研究科, 教授 (50134622)
Keywords造血幹細胞 / ニッシェ / ホーミング / ES細胞 / ATM / ポリコーム遺伝子産物 / 自己複製 / 未分化性維持機構
Research Abstract

計画研究代表者9名および39件の公募研究の代表者を加えて、申請書に計画研究にあった通り、1)細胞の初期化の機構、2)幹細胞の未分化性維持機構、3)幹細胞の多様性と可塑性の3つの課題について研究が進められた。
3年目に入り以下のような研究成果が得られている。
1.マウスのES細胞を無血清、無フィーダー細胞で培養できる系の確立。
2.骨髄ニッシェにおけるAng-1-Tie-2を介した造血幹細胞の保護機構
3.造血幹細胞の数と能力を負に制御する細胞内アダプターたんぱく質Lnkの発見
4.造血幹細胞分離方法の確立と造血幹細胞の高いホーミング能
5.カドミウム処理と精細管内への精巣細胞移植による精子幹細胞ニッシェの再構成法の確立
6.細胞周期チェックポイント分子ATM (Ataxia Telangiectasia Mutated)による造血幹細胞の自己複製維持機構
7.ポリコーム群タンパクBmi-1による造血幹細胞、神経幹細胞、精子幹細胞に共通な自己複製制御機構の解明
8.膵臓における多能性前駆細胞の同定
昨年4月ならびに本年2月に公開班会議を開催し、計画研究代表者および公募研究代表者全員が研究成果を発表し、活発な討論が行われた。公開班会議以外でも幹細胞や再生医学関する学会、シンポジウムが国内外で数多く開催されていて、班員間の研究交流も極めて活発に行われている。本年11月にはES細胞に関する国際シンポジウムを開催する予定である。
二回目の公募研究募集には209件の申請があり、およそ40件の研究課題を採択した。本年4月より新たなメンバーによって研究が開始される予定である。

  • Research Products

    (58 results)

All 2005 2004

All Journal Article (58 results)

  • [Journal Article] Mouse epiblast changes responsiveness to BMP4 signal required for PGC formation by the functions of extraembryonic ectoderm.2005

    • Author(s)
      Okamura D.et al.
    • Journal Title

      Mol.Reprod.Dev. 70

      Pages: 20-29

  • [Journal Article] H.A novel mechanism for regulating clonal propagation of mouse ES cells.2004

    • Author(s)
      Ogawa K.et al.
    • Journal Title

      Genes to Cells. 9

      Pages: 471-477

  • [Journal Article] Nuclear transfer of adult bone marrow mesenchymal stem cells Developmental totipotency of tissue-specific stem cells from an adult mammal.2004

    • Author(s)
      Kato Y.et al.
    • Journal Title

      Biol.Reprod. 70

      Pages: 415-418

  • [Journal Article] Comparison of in vitro development of porcine nuclear transferred oocytes receiving fetal somatic cells by injection and fusion methods.2004

    • Author(s)
      Kawano K, et al.
    • Journal Title

      Cloning and Stem Cells. 6

      Pages: 67-72

  • [Journal Article] Effect of nuclear transfer procedures on ES-cell cloning efficiency in the mouse2004

    • Author(s)
      Yabuuchi A.et al.
    • Journal Title

      J.Reprod.Dev. 50

      Pages: 263-268

  • [Journal Article] Effect of the timing of the first cleavage on the developmental potential of nuclear transferred mouse oocytes receiving embryonic stem cells.2004

    • Author(s)
      Kobayashi T, et al.
    • Journal Title

      Theriogenology. 62

      Pages: 854-860

  • [Journal Article] Histone code modifications on pluripotential nuclei of reprogrammed somatic cells.2004

    • Author(s)
      Tada M.et al.
    • Journal Title

      Mol.Cell.Biol. 24

      Pages: 5710-5720

  • [Journal Article] Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting.2004

    • Author(s)
      Kaneda M.et al.
    • Journal Title

      Nature. 429

      Pages: 990-903

  • [Journal Article] The Sox-2 regulatory regions display their activities in two distinct types of multipotent stem cells.2004

    • Author(s)
      Miyagi S, et al.
    • Journal Title

      Mol.Cell.Biol. 24

      Pages: 4207-4220

  • [Journal Article] Slx1 controls patterning of the mouse otic vesicle.2004

    • Author(s)
      Ozaki H.et al.
    • Journal Title

      Development. 131

      Pages: 551-562

  • [Journal Article] Essential roles of Meltrin β (ADAM19) in heart development.2004

    • Author(s)
      Kurohara K.et al.
    • Journal Title

      Dev.Biol. 267

      Pages: 14-28

  • [Journal Article] Hepatocyte growth factor controls proliferation of cultured epiderma melanoblasts and melanocytes from new born.2004

    • Author(s)
      Hirobe T.et al.
    • Journal Title

      Pigment Cell Res. 17

      Pages: 51-61

  • [Journal Article] Granulocyte-macrophage colony-stimulating factor is a kelatinocyte-derived factor involved in regulating the proliferation and differentiation of neonatal mouse epidermal melanocytes in culture2004

    • Author(s)
      Hirobe T.et al.
    • Journal Title

      Exp.Cell Res. 297

      Pages: 593-606

  • [Journal Article] Retinoic-acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells.2004

    • Author(s)
      Okada Y.et al.
    • Journal Title

      Dev.Biol. 275

      Pages: 142-142

  • [Journal Article] Downregulation of STAT3 activation is required for presumptive rod photoreceptor cells to differentiate in the postnatal2004

    • Author(s)
      Ozawa Y.et al.
    • Journal Title

      Mol.Cell.Neurosci. 26

      Pages: 288-270

  • [Journal Article] Meteorin : a secreted protein that regulates gilial cell differentiation and promotes axonal extension.2004

    • Author(s)
      Nishino J. et al.
    • Journal Title

      EMBO J. 23

      Pages: 1998-2008

  • [Journal Article] Unexpectedly efficient homing capacity of purified murine hematopoietic stem cell.2004

    • Author(s)
      Matsuzaki Y.et al.
    • Journal Title

      Immunity. 20

      Pages: 87-93

  • [Journal Article] The cell cycle regulator Geminin inhibits lox function via direct and Polycomb-mediated interactions.2004

    • Author(s)
      Luo L.et al.
    • Journal Title

      Nature. 427

      Pages: 749-752

  • [Journal Article] Common chromosome aberrations in immortalized normal foreskin fibroblast cultures following transduction of Cyclin A2 or Cdk1 gene in retroviral vectors.2004

    • Author(s)
      Tresini M.et al.
    • Journal Title

      Exp.Cell Res. 294

      Pages: 406-419

  • [Journal Article] A novel partner gene CIP29 containing a SAP domain with MLL identified in infantile myelomonocytic leukemia.2004

    • Author(s)
      Hashi, Y.et al.
    • Journal Title

      Leukemia. 18

      Pages: 1546-1548

  • [Journal Article] CD9 is a surface marker on mouse and rat male germline stem cells.2004

    • Author(s)
      Kanatsu-Shinohara M.et al.
    • Journal Title

      Biol.Reprod. 70

      Pages: 70-75

  • [Journal Article] Regulation of mouse spermatogonial stem cell self-renewing division by the pituitary gland.2004

    • Author(s)
      Kanatsu-Shinohara M.et al.
    • Journal Title

      Biol.Reprod. 70

      Pages: 1731-1737

  • [Journal Article] Transgenic mouse produced by retroviral transduction of male Germ line stem cells in vivo.2004

    • Author(s)
      Kanatsu-Shinohara M.et al.
    • Journal Title

      Biol.Reprod. 71

      Pages: 1202-1207

  • [Journal Article] In vivo and in vitro constant expression of GATA-4 in mouse postnata Sertoli cells.2004

    • Author(s)
      Imai T.et al.
    • Journal Title

      Mol Cellular Endocrinol. 214

      Pages: 107-115

  • [Journal Article] Abnormal angiogenesis in Foxo1 (FKHR)-deficient mice.2004

    • Author(s)
      Furuyama T.et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 34741-34749

  • [Journal Article] Increased Numbers of B-1 cells and Enhanced Responses against Ti-2 Antigen in Mice Lacking APS, an Adaptor Molecule Containing PH and SH2 Domains.2004

    • Author(s)
      Iseki M.et al.
    • Journal Title

      Mol.Cell.Biol. 24

      Pages: 2243-2250

  • [Journal Article] A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage.2004

    • Author(s)
      Nakayama N.et al.
    • Journal Title

      Development. 131

      Pages: 229-240

  • [Journal Article] Impaired IgG production in mice deficient for heat shock transcription factor 1.2004

    • Author(s)
      Inouye S. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 38701-38709

  • [Journal Article] Embryonic stem cells are capable of generating a neuronal network in the adult mouse retina.2004

    • Author(s)
      Hara A.et al.
    • Journal Title

      Brain Res. 999

      Pages: 216-221

  • [Journal Article] c-Kit-targeting immunotherapy for hereditary melanoma in a mouse model.2004

    • Author(s)
      Kato M.et al.
    • Journal Title

      Cancer Res. 64

      Pages: 801-806

  • [Journal Article] Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas.2004

    • Author(s)
      Horie Y.et al.
    • Journal Title

      J.Clin.Invest. 113

      Pages: 1774-1783

  • [Journal Article] Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten.2004

    • Author(s)
      Backman SA.et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101

      Pages: 1725-1730

  • [Journal Article] PI3-kinase-Medeated Activation of Cofilin Phosphatase Slingshot-1L Controls Inslin-induced Membrane Protrusion.2004

    • Author(s)
      Nishita M.et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 7193-7198

  • [Journal Article] Human placenta-derived cells have mesenchymal stem/progenitor cell potential.2004

    • Author(s)
      Fukuchi Y.et al.
    • Journal Title

      Stem Cells. 22

      Pages: 649-658

  • [Journal Article] Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche.2004

    • Author(s)
      Arai F.et al.
    • Journal Title

      Cell. 118

      Pages: 149-161

  • [Journal Article] Collaboration of Brca1 and Chk2 in tumorigenesis.2004

    • Author(s)
      McPherson J.P.et al.
    • Journal Title

      Genes Dev. 18

      Pages: 1144-1153

  • [Journal Article] Endothelin-1 regulates the dorsoventral branchial arch patterning in mice.2004

    • Author(s)
      Ozeki, H.et al.
    • Journal Title

      Mechanisms of Development. 121

      Pages: 387-395

  • [Journal Article] Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression.2004

    • Author(s)
      Ieda M.et al.
    • Journal Title

      J.Clin.Invst. 113

      Pages: 876-884

  • [Journal Article] Asymmetric division and lineage commitment at the level of hematopoietic stem cells : inference from differentiation in daughter cell and granddaughter cell pairs.2004

    • Author(s)
      Takano H.et al.
    • Journal Title

      J Exp Med. 199

      Pages: 295-302

  • [Journal Article] "Homing to Niche," a new criterion for hematopoietic stem cells?2004

    • Author(s)
      Ema H.et al.
    • Journal Title

      Immunity 20

      Pages: 1-2

  • [Journal Article] Conversion of biliary system to pancreatic tissue in Hes1-deficient mice.2004

    • Author(s)
      Sumazaki R.et al.
    • Journal Title

      Nat Genet. 6

      Pages: 83-87

  • [Journal Article] Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting.2004

    • Author(s)
      Suzuki A.et al.
    • Journal Title

      Diabetes. 53

      Pages: 2143-2152

  • [Journal Article] The Sox-2 regulatory regions display their activities in two distinct types of multipotent stem cells.2004

    • Author(s)
      Miyagi S.et al.
    • Journal Title

      Mol Cell Biol. 24

      Pages: 4207-4220

  • [Journal Article] Molecular and clinical basis for the regeneration of human gastrointestinal epithelia.2004

    • Author(s)
      Okamoto R.et al.
    • Journal Title

      J Gastroenterol. 39

      Pages: 1-6

  • [Journal Article] Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene express and production of interleukin-7 in human intestinal epithelial cells.2004

    • Author(s)
      Oshima S.et al.
    • Journal Title

      Mol Cell Biol. 24

      Pages: 6298-6310

  • [Journal Article] Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of TIE2 signaling in vascular progenitor cells.2004

    • Author(s)
      Suzuki Y.et al.
    • Journal Title

      Blood. 104

      Pages: 166-169

  • [Journal Article] Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db mice.2004

    • Author(s)
      Aoki K.et al.
    • Journal Title

      Life Sciences. 74

      Pages: 3075-3084

  • [Journal Article] Preferential expression of the vasoactive intestinal peptide (VIP) receptor VPAC1 in human cord blood-derived CD34^+CD38^- cells : possible role of VIP as a growth-promoting factor for hepatopoiet stem/progenitor cells.2004

    • Author(s)
      Kawakami, M.
    • Journal Title

      Leukemia. 18

      Pages: 912-921

  • [Journal Article] Pyrazolo pyrimidine-type inhibitors of src family tyrosine kinases promote ovarian steroid-induced differentiation of human endometrial stromal cells in vitro.2004

    • Author(s)
      Maruyama T.et al.
    • Journal Title

      Biol Reprod. 70

      Pages: 214-221

  • [Journal Article] Rapid replacement of somatic linker histones with the oocyte-specific linker histone H1foo in nuclear transfer.2004

    • Author(s)
      Teranishi T.et al.
    • Journal Title

      Dev.Biol. 266

      Pages: 76-86

  • [Journal Article] Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction.2004

    • Author(s)
      Kawada H.et al.
    • Journal Title

      Blood. 104

      Pages: 3581-3587

  • [Journal Article] Cloning of cDNA encoding a regeneration-associated muscle protease whose expression is attenuated in cell lines derived from Duchenne muscular dystrophy patients.2004

    • Author(s)
      Nakayama Y. et al.
    • Journal Title

      Am.J.Pathol. 164

      Pages: 1773-1782

  • [Journal Article] Expression and the biological activities of insulin-like growth factor-binding protein related protein 1 (IGFBP-rP1/mac25) in rat uterus during the pen-implantation period.2004

    • Author(s)
      Tamura K.et al.
    • Journal Title

      Endocrinol. 145

      Pages: 5243-5251

  • [Journal Article] Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice2004

    • Author(s)
      Sakurai K.et al.
    • Journal Title

      Gene Therapy. 11

      Pages: 1475-1481

  • [Journal Article] Expression of a Novel Human Gene, Human Wings Apart-Like (hWAPL), Is Associated with Cervical Carcinogenesis and Tumor Progression.2004

    • Author(s)
      Oikawa K.et al.
    • Journal Title

      Cancer Res. 64

      Pages: 3545-3549

  • [Journal Article] Developmental totipotency of tissue-specific stem cells from an adult mammal Nuclear transfer of adult bone marrow mesenchymal stem cells.2004

    • Author(s)
      Kato Y.et al.
    • Journal Title

      Biol Reprod. 70

      Pages: 415-418

  • [Journal Article] Hrp48 regulates couples oskar mRNA localization and translational control during Drosophila oogenesis.2004

    • Author(s)
      Yano T.et al.
    • Journal Title

      Dev.Cell. 6

      Pages: 637-648

  • [Journal Article] Regulation of expression of mouse interferon-induced transmembrane protein like gene-1, Ifitm3 (mil-1/fragilis), in germ cells.2004

    • Author(s)
      Tanaka S.S.et al.
    • Journal Title

      Dev.Dyn. 231

      Pages: 651-659

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Published: 2006-07-12   Modified: 2016-04-21  

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