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2011 Fiscal Year Final Research Report

Molecular mechanisms underlying nuclear reprogramming of somatic cells

Research Project

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Project/Area Number 19002014
Research Category

Grant-in-Aid for Specially Promoted Research

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

Principal Investigator

YAMANAKA Shinya  京都大学, iPS細胞研究所, 教授 (10295694)

Co-Investigator(Kenkyū-buntansha) AOI Takashi  京都大学, iPS細胞研究所, 教授 (00546997)
NAKAGAWA Masato  京都大学, iPS細胞研究所, 講師 (10379539)
TAKAHASHI Kazutoshi  京都大学, iPS細胞研究所, 講師 (80432326)
OKITA Keisuke  京都大学, iPS細胞研究所, 講師 (90512434)
YOSHIDA Yoshinori  京都大学, iPS細胞研究所, 特定拠点講師 (20447965)
WATANABE Akira  京都大学, iPS細胞研究所, 特定拠点助教 (60506765)
YAMAMOTO Takuya  京都大学, iPS細胞研究所, 特定拠点助教 (60546993)
KNUT Woltjen  京都大学, iPS細胞研究所, 特定拠点助教 (50589489)
KOYANAGI Michiyo  京都大学, iPS細胞研究所, 特定研究員 (90432327)
Project Period (FY) 2007 – 2011
Keywords再生医学 / 幹細胞 / 分化多能性 / 核初期化 / 転写因子
Research Abstract

iPS cells can be generated by introduction of four reprogramming factors into somatic cells. We have found that chimera mice produced with c-Myc show high tumorigenicity. To overcome this issue, we could generate iPS cells without Myc under the modified conditions. But Myc minus iPS cells showed less pluripotency compared to iPS cells generated with c-Myc. Next, we explored the factors which could replace the c-Myc function. We found L-Myc as a candidate. We could confirm that L-Myc enhances the efficiency of iPS generation and that the tumorigenicity of L-Myc is hardly observed. So, we can obtain the safer iPS cells using L-Myc. We established the system to examine the safety of iPS cells using the iPS cells-derived neuronal cells. We also established the differentiation methods of iPS cells into hepatocytes, blood cells, and cardiomyocytes in vitro. Next generation sequencer(NGS) is very powerful tool for analysis of genetic properties of iPS cells. We have analyzed the gene expression, DNA methylation, changes of splicing pattern in iPS cells using NGS

  • Research Products

    (36 results)

All 2012 2011 2010 2009 2008 2007 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (11 results) Remarks (1 results) Patent(Industrial Property Rights) (7 results) (of which Overseas: 5 results)

  • [Journal Article] Essential roles of ECAT15-2/Dppa2 in functional lung development2011

    • Author(s)
      Nakamura, T., et al.(他4名、1番目)
    • Journal Title

      Mol Cell Biol

      Volume: 31(21) Pages: 4366-4378

    • Peer Reviewed
  • [Journal Article] Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis12011

    • Author(s)
      Maekawa, M., et al.(他9名、1番目)
    • Journal Title

      Nature

      Volume: 474(7350) Pages: 225-229

    • Peer Reviewed
  • [Journal Article] ECAT11/L1td1 is enriched in ESCs and rapidly activated during iPSC generation, but it is dispensable for the pluripotency2011

    • Author(s)
      Iwabuchi, K., et al.(他6名、1番目)
    • Journal Title

      PLoS ONE

      Volume: 6(5) Pages: e20461

    • Peer Reviewed
  • [Journal Article] A more efficient method to generate integration-free human iPS cells2011

    • Author(s)
      Okita, K., et al.(他15名、1番目)
    • Journal Title

      Nat Methods

      Volume: 8(5) Pages: 409-412

    • Peer Reviewed
  • [Journal Article] Promotion of direct reprogramming by transformation-deficient Myc2010

    • Author(s)
      Nakagawa, M., et al.(他4名、1番目)
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 107(32) Pages: 14152-14157

    • Peer Reviewed
  • [Journal Article] Generation of mouse-induced pluripotent stem cells with plasmid vectors2010

    • Author(s)
      Okita, K., et al.(他3名、1番目)
    • Journal Title

      Nat Protoc

      Volume: 5(3) Pages: 418-428

    • Peer Reviewed
  • [Journal Article] Human induced pluripotent stem cells on autologous feeders2009

    • Author(s)
      Takahashi, K., et al.(他4名、1番目)
    • Journal Title

      PLoS ONE

      Volume: 4(12) Pages: e8067

    • Peer Reviewed
  • [Journal Article] Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells2009

    • Author(s)
      Yoshida, Y., et al.(他4名、1番目)
    • Journal Title

      Cell Stem Cell

      Volume: 5(3) Pages: 237-241

    • Peer Reviewed
  • [Journal Article] Suppression of induced pluripotent stem cell generation by the p53-p21 pathway2009

    • Author(s)
      Hong, H., et al.(他7名、1番目)
    • Journal Title

      Nature

      Volume: 460(7259) Pages: 1132-1135

    • Peer Reviewed
  • [Journal Article] Variation in the safety of induced pluripotent stem cell lines2009

    • Author(s)
      Miura, K., et al.(他13名、1番目)
    • Journal Title

      Nat Biotechnol

      Volume: 27(8) Pages: 743-745

    • Peer Reviewed
  • [Journal Article] Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts2009

    • Author(s)
      Tsubooka, N., et al.(他5名、1番目)
    • Journal Title

      Genes Cells

      Volume: 14(6) Pages: 683-694

    • Peer Reviewed
  • [Journal Article] Generation of mouse induced pluripotent stem cells without viral vectors2008

    • Author(s)
      Okita, K., et al.(他4名、1番目)
    • Journal Title

      Science

      Volume: 322(5903) Pages: 949-953

    • Peer Reviewed
  • [Journal Article] Generation of pluripotent stem cells from adult mouse liver and stomach cells2008

    • Author(s)
      Aoi, T., et al.(他7名、1番目)
    • Journal Title

      Science

      Volume: 321 Pages: 699-702

    • Peer Reviewed
  • [Journal Article] Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts2008

    • Author(s)
      Nakagawa, M., et al.(他9名、1番目)
    • Journal Title

      Nat Biotechnol

      Volume: 26 Pages: 101-106

    • Peer Reviewed
  • [Journal Article] Induction of pluripotent stem cells from fibroblast cultures2007

    • Author(s)
      Takahashi, K., et al.(他3名、1番目)
    • Journal Title

      Nat Protoc

      Volume: 2 Pages: 3081-3089

    • Peer Reviewed
  • [Journal Article] Induction of pluripotent stem cells from adult human fibroblasts by defined factors2007

    • Author(s)
      Takahashi, K., et al.(他6名、1番目)
    • Journal Title

      Cell

      Volume: 131 Pages: 861-872

    • Peer Reviewed
  • [Journal Article] Generation of germline-competent induced pluripotent stem cells2007

    • Author(s)
      Okita, K., et al.(他2名、1番目)
    • Journal Title

      Nature

      Volume: 448 Pages: 313-317

    • Peer Reviewed
  • [Presentation] Induction of Pluripotency by Defined Factors2012

    • Author(s)
      Yamanaka, S.
    • Organizer
      Keystone Symposia 2012 Cardiovascular Development and Regeneration
    • Place of Presentation
      タオス(アメリカ)
    • Year and Date
      2012-01-22
  • [Presentation] 偶然と幸運から生まれたiPS細胞2011

    • Author(s)
      山中伸弥
    • Organizer
      第34回分子生物学会年会日本分子生物学会若手教育シンポジウム若手教育ランチョンセミナー
    • Place of Presentation
      東京
    • Year and Date
      2011-12-01
  • [Presentation] Induction of Pluripotency by Defined Factors2011

    • Author(s)
      Yamanaka, S.
    • Organizer
      ISSCR 9th Annual Meeting
    • Place of Presentation
      トロント(カナダ)
    • Year and Date
      2011-06-17
  • [Presentation] Induction of Pluripotency by Defined Factors2010

    • Author(s)
      Yamanaka, S.
    • Organizer
      ISSCR 8th Annual Meeting
    • Place of Presentation
      サンフランシスコ(アメリカ)
    • Year and Date
      2010-06-16
  • [Presentation] iPS細胞の可能性と課題2010

    • Author(s)
      山中伸弥
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-19
  • [Presentation] Induction of Pluripotency by Defined Factors2009

    • Author(s)
      山中伸弥
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      神奈川
    • Year and Date
      2009-12-09
  • [Presentation] Induction of Pluripotency by Defined Factors2009

    • Author(s)
      Yamanaka, S.
    • Organizer
      ISSCR 7th Annual Meeting
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2009-07-11
  • [Presentation] PS細胞の可能性と課題2009

    • Author(s)
      山中伸弥
    • Organizer
      第8回日本再生医療学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-03-05
  • [Presentation] 多能性総論2008

    • Author(s)
      山中伸弥
    • Organizer
      第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(BMB2008)シンポジウム
    • Place of Presentation
      兵庫
    • Year and Date
      2008-12-09
  • [Presentation] Generation of iPS cells from adult human fibroblasts2008

    • Author(s)
      Yamanaka, S.
    • Organizer
      Keystone Symposia "Signaling Passways in Cancer and Development"
    • Place of Presentation
      スティームボートスプリングス(アメリカ)
    • Year and Date
      2008-03-25
  • [Presentation] 人工万能幹(iPS)細胞の可能性と課題2008

    • Author(s)
      山中伸弥
    • Organizer
      第7回日本再生医療学会総会
    • Place of Presentation
      愛知
    • Year and Date
      2008-03-14
  • [Remarks]

    • URL

      http://www.cira.kyoto-u.ac.jp/j/index.html

  • [Patent(Industrial Property Rights)] Nuclear Reprogramming Factor and Induced Pluripotent Stem cells Induced Pluripotent Stem cells2011

    • Inventor(s)
      山中伸弥、高橋和利、他
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、8129187
    • Acquisition Date
      2011-12-27
    • Overseas
  • [Patent(Industrial Property Rights)] Nuclear Reprogramming Factor and Induced Pluripotent Stem cells2011

    • Inventor(s)
      山中伸弥、高橋和利
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、8058065
    • Acquisition Date
      2011-11-15
    • Overseas
  • [Patent(Industrial Property Rights)] Nuclear Reprogramming Method2011

    • Inventor(s)
      山中伸弥、高橋和利、中川誠人
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、0153139
    • Acquisition Date
      2011-06-15
    • Overseas
  • [Patent(Industrial Property Rights)] 誘導多能性細胞からの体細胞の製造方法2009

    • Inventor(s)
      山中伸弥
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、4411363
    • Acquisition Date
      2009-11-20
  • [Patent(Industrial Property Rights)] 誘導多能性幹細胞の製造方法2009

    • Inventor(s)
      山中伸弥
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、4411362
    • Acquisition Date
      2009-11-20
  • [Patent(Industrial Property Rights)] 誘導多能性幹細胞の製造方法2008

    • Inventor(s)
      山中伸弥
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、4183742
    • Acquisition Date
      2008-09-21
    • Overseas
  • [Patent(Industrial Property Rights)] Genes with ES Cell-specific Expression2007

    • Inventor(s)
      山中伸弥
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      特許、US7250255
    • Acquisition Date
      2007-07-31
    • Overseas

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Published: 2013-07-31  

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