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2009 Fiscal Year Final Research Report

Analyses on the degradation of Hes, a transcription factor, regulates timings of cellular differentiation

Research Project

  • PDF
Project/Area Number 20770100
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionKyoto University

Principal Investigator

KOBAYASHI Taeko  Kyoto University, ウイルス研究所, 助教 (40402804)

Project Period (FY) 2008 – 2009
Keywords細胞内タンパク質分解 / 転写因子の発現振動(オシレーション)
Research Abstract

The basic helix-loop-helix (bHLH) gene Hes is expressed in an oscillatory manner and regulates the differentiation timings at developmental stages. Oscillatory expression of Hes depends on rapid degradation of the gene products, but the precise mechanisms of both how the degradation of Hes protein are regulated and how the timings of cell differentiation are regulated by Hes oscillation remain unclear. First, we found that some lysine residues are essential not only for the instability of Hes7 protein but also for the transcriptional repressor activity. Second, we found that expression of Hes1 oscillates in mouse embryonic stem (ES) cells every 3-5 hours. ES cells expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. We revealed that the cyclic expression of Hes1 gene contributes to heterogeneous differentiation of homogenous ES cell populations.

  • Research Products

    (23 results)

All 2010 2009 2008 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (12 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling.2010

    • Author(s)
      小林妙子、影山龍一郎
    • Journal Title

      Genes Cells (accepted)

    • Peer Reviewed
  • [Journal Article] Hes1 oscillation: making variable choices for stem cell differentiation.2010

    • Author(s)
      小林妙子、影山龍一郎
    • Journal Title

      Cell Cycle 9巻

      Pages: 207-208

    • Peer Reviewed
  • [Journal Article] The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.2009

    • Author(s)
      小林妙子、水野浩彰、今吉格、古澤力、白髭克彦、影山龍一郎
    • Journal Title

      Genes and Development 23巻

      Pages: 1870-1875

    • Peer Reviewed
  • [Journal Article] Dynamic advances in NF-kappaB signaling analysis.2009

    • Author(s)
      小林妙子、影山龍一郎
    • Journal Title

      Science Signaling 2巻

      Pages: e47

    • Peer Reviewed
  • [Journal Article] Roles of Hes genes in neural development.2008

    • Author(s)
      影山龍一郎、大塚俊之、小林妙子
    • Journal Title

      Dev Growth Differ. 50巻

      Pages: S97-103

    • Peer Reviewed
  • [Journal Article] Requirement of multiple lysine residues for the transcriptional activity and the instability of Hes7.2008

    • Author(s)
      石井章子、小林妙子、影山龍一郎
    • Journal Title

      Biochem Biophys Res Commun. 372巻

      Pages: 142-146

    • Peer Reviewed
  • [Presentation] 理研シンポジウム「細胞システムの動態と論理II」(振動遺伝子Hes1によるES細胞の分化調節機構(招待講演))2010

    • Author(s)
      小林妙子
    • Organizer
      独立行政法人理化学研究所・和光
    • Year and Date
      20100408-20100409
  • [Presentation] CDB Symposium 2010, Frontiers in Organogenesis2010

    • Author(s)
      小林妙子
    • Organizer
      The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.
    • Place of Presentation
      理化学研究所発生・再生科学総合研究センター
    • Year and Date
      20100323-20100325
  • [Presentation] Keystone Symposia, Stem Cell Differentiation and Dedifferentiation2010

    • Author(s)
      小林妙子
    • Organizer
      The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.
    • Place of Presentation
      Keystone Resort, Colorado, USA
    • Year and Date
      20100215-20100220
  • [Presentation] 振動遺伝子Hes1が胚性幹細胞の多様な分化応答に寄与する2010

    • Author(s)
      小林妙子
    • Organizer
      第2回定量生物の会
    • Place of Presentation
      大阪大学
    • Year and Date
      20100110-20100111
  • [Presentation] The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.2009

    • Author(s)
      小林妙子
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      20091021-20091024
  • [Presentation] MicroRNA-9 regulates the timing of neural stem cell differentiation by fine-tuning Hes1 expression in the developing cortex.2009

    • Author(s)
      Tan, S.L. 、小林妙子
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      20091021-20091024
  • [Presentation] The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.2009

    • Author(s)
      小林妙子
    • Organizer
      The international symposium on complex systems biology
    • Place of Presentation
      東京大学
    • Year and Date
      20090929-20091001
  • [Presentation] 転写因子Hes1の発現振動が胚性幹細胞の多様な分化応答に寄与する(招待講演)2009

    • Author(s)
      小林妙子
    • Organizer
      神戸薬科大学研究セミナー
    • Place of Presentation
      神戸薬科大学
    • Year and Date
      2009-10-15
  • [Presentation] The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells(招待講演)2009

    • Author(s)
      小林妙子
    • Organizer
      大学院教育コース再生医療・臓器再建コースミーティング
    • Place of Presentation
      京都大学
    • Year and Date
      2009-10-09
  • [Presentation] The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells(招待講演)2009

    • Author(s)
      小林妙子
    • Organizer
      大学院教育コース発生・細胞生物学コースミーティング
    • Place of Presentation
      京都大学
    • Year and Date
      2009-07-24
  • [Presentation] マウス胚性幹(ES)細胞におけるHes1の発現振動2009

    • Author(s)
      小林妙子
    • Organizer
      第1回定量生物の会
    • Place of Presentation
      東京大学
    • Year and Date
      2009-01-11
  • [Presentation] Hes1 oscillations contribute to diverse differentiation response of embryonic stem cells(招待講演)2008

    • Author(s)
      小林妙子
    • Organizer
      大学院教育コース[発生・形態形成学・生殖医学]ミーティング
    • Place of Presentation
      京都大学
    • Year and Date
      2008-07-02
  • [Book] 神経の分化、回路形成、機能発現2008

    • Author(s)
      影山龍一郎、小林妙子, 他
    • Total Pages
      318-323
    • Publisher
      共立出版
  • [Remarks] ・研究室ホームページ

    • URL

      http://www.virus.kyoto-u.ac.jp/Lab/Kageyama/index.html

  • [Remarks]

    • URL

      http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2009/090815_1.htm

  • [Remarks]

    • URL

      http://www.virus.kyoto-u.ac.jp/

  • [Patent(Industrial Property Rights)] 多能性幹細胞からの神経細胞の分化誘導方法2009

    • Inventor(s)
      小林妙子、影山龍一郎
    • Industrial Property Rights Holder
      京都大学
    • Industrial Property Number
      特願・2009-168045
    • Filing Date
      2009-07-16

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Published: 2011-06-18   Modified: 2016-04-21  

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