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2016 Fiscal Year Annual Research Report

Gene regulatory network underlying epiblast cell determination and their derivation into various somatic cell lineages

Research Project

Project/Area Number 26251024
Research InstitutionKyoto Sangyo University

Principal Investigator

近藤 寿人  京都産業大学, 総合生命科学部, 教授 (70127083)

Project Period (FY) 2014-04-01 – 2017-03-31
Keywords遺伝子発現調節 / エピブラスト幹細胞 / マウス胚操作 / 体細胞系列 / ノード
Outline of Annual Research Achievements

すべての体細胞系列の直接の前駆体であるエピブラストから、個々の体細胞系列がどのような制御のもとで生み出されたり分岐したりするのかという発生生物学の基本問題について研究した。次の成果を得た。
1.エピブラスト幹細胞における主要な5つの転写因子Zic2, Otx2, Sox2, Pou5f1, Pou3f1のゲノム上の結合部位を網羅的に明らかにするChIP-seq解析を行った。これまでSox2-Pou5f1の2転写因子の複合体が初期胚幹細胞に共通して、主要な制御機能を担うと考えられてきたが、それは誤りであった。Sox2-Pou5f1は着床前胚の状態に対応するマウスES細胞のみで転写制御の中心を占めるが、着床直後の胚に対応するエピブラスト幹細胞などではSox2-Pou5f1に代わってZic2-Otx2転写因子ペアが主要な転写制御の役割を担う。この主要な転写因子ペアの交代が、体細胞系列の発生を準備する過程である。
2.ニワトリ胚のエピブラストは、先ずOtx2の有無によって前部と後部に分けられる。蛍光標識したノードを宿主胚に異所移植してライブイメージングで解析した。胚の前半に移植されたノードは、前部中内胚葉を生み出し、その新たに生み出された前部中内胚葉の周りに宿主エピブラストが集合して、新たな頭部構造を作ることがわかった。
3.エピブラスト幹細胞から直接に神経幹細胞株を樹立する際のWntシグナルの強度の影響を調べた。低Wntの条件で樹立すると、Otx2+, Hox-の頭部神経系の幹細胞が得られたのに対して、Wnt無操作の条件ではOtx2-, Hox+の前部脊髄の幹細胞が得られ、その性質は安定に維持された。
4.内胚葉の領域化にはSox2が関与している。内胚葉特異的にSox2をノックアウトすると、食道の内胚葉由来上皮が気管上皮に変化するだけでなく、上皮を取り巻く間充織も気管のものに変化した。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

  • Research Products

    (36 results)

All 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (20 results) (of which Int'l Joint Research: 12 results,  Invited: 2 results) Remarks (4 results)

  • [Int'l Joint Research] Emory University of Medicine/Albert Einstein College of Medicine(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Emory University of Medicine/Albert Einstein College of Medicine
  • [Int'l Joint Research] Tel-Aviv University/Hebrew University of Jerusalem(Israel)

    • Country Name
      Israel
    • Counterpart Institution
      Tel-Aviv University/Hebrew University of Jerusalem
  • [Int'l Joint Research] Katholieke Universiteit Leuven(Belgium)

    • Country Name
      Belgium
    • Counterpart Institution
      Katholieke Universiteit Leuven
  • [Int'l Joint Research] Erasmus University Medical Center(オランダ)

    • Country Name
      NETHERLANDS
    • Counterpart Institution
      Erasmus University Medical Center
  • [Journal Article] Roles of ZIC2 in Regulation of Pluripotent Stem Cells2018

    • Author(s)
      Kondoh Hisato
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1046 Pages: 339~351

    • DOI

      10.1007/978-981-10-7311-3_17

    • Peer Reviewed
  • [Journal Article] Nasal and otic placode specific regulation of Sox2 involves both activation by Sox-Sall4 synergism and multiple repression mechanisms2018

    • Author(s)
      Sugahara Satoko、Fujimoto Tooru、Kondoh Hisato、Uchikawa Masanori
    • Journal Title

      Dev. Biol.

      Volume: 433 Pages: 61~74

    • DOI

      10.1016/j.ydbio.2017.11.005

    • Peer Reviewed
  • [Journal Article] Enhancer analyses using chicken embryo electroporation2017

    • Author(s)
      Uchikawa Masanori、Nishimura Naoko、Iwafuchi-Doi Makiko、Kondoh Hisato
    • Journal Title

      Methods Mol Biol.

      Volume: 1650 Pages: 191~202

    • DOI

      10.1007/978-1-4939-7216-6_12

    • Peer Reviewed
  • [Journal Article] ChIP-seq analysis of genomic binding regions of five major transcription factors highlights a central role for ZIC2 in the mouse epiblast stem cell gene regulatory network2017

    • Author(s)
      Matsuda Kazunari、Mikami Tomoyuki、Oki Shinya、Iida Hideaki、Andrabi Munazah、Boss Jeremy M.、Yamaguchi Katsushi、Shigenobu Shuji、Kondoh Hisato
    • Journal Title

      Development

      Volume: 144 Pages: 1948~1958

    • DOI

      10.1242/dev.143479

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation2017

    • Author(s)
      Iida Hideaki、Ishii Yasuo、Kondoh Hisato
    • Journal Title

      Dev. Bill.

      Volume: 421 Pages: 118~125

    • DOI

      10.1016/j.ydbio.2016.11.004

    • Peer Reviewed
  • [Journal Article] Sip1 regulates the generation of the inner nuclear layer retinal cell lineages in mammals2016

    • Author(s)
      Menuchin-Lasowski Yotam、Oren-Giladi Pazit、Xie Qing、Ezra-Elia Raaya、Ofri Ron、Peled-Hajaj Shany、Farhy Chen、Higashi Yujiro、Van de Putte Tom、Kondoh Hisato、Huylebroeck Danny、Cvekl Ales、Ashery-Padan Ruth
    • Journal Title

      Development

      Volume: 143 Pages: 2829~2841

    • DOI

      10.1242/dev.136101

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate2016

    • Author(s)
      Kondoh Hisato、Takada Shinji、Takemoto Tatsuya
    • Journal Title

      Dev. Growth. Differ.

      Volume: 58 Pages: 427~436

    • DOI

      10.1111/dgd.12295

    • Peer Reviewed
  • [Journal Article] R26-WntVis reporter mice showing graded response to Wnt signal levels2016

    • Author(s)
      Takemoto Tatsuya、Abe Takaya、Kiyonari Hiroshi、Nakao Kazuki、Furuta Yasuhide、Suzuki Hitomi、Takada Shinji、Fujimori Toshihiko、Kondoh Hisato
    • Journal Title

      Genes Cells

      Volume: 21 Pages: 661~669

    • DOI

      10.1111/gtc.12364

    • Peer Reviewed / Open Access
  • [Presentation] SOX2-dependent determination of tissue identity in the foregut.2017

    • Author(s)
      Teramoto M, Sugawara R, Ishii Y, Kuroiwa A, Kondoh H.
    • Organizer
      ConBio2017
  • [Presentation] A drastic change in the major regulatory TFs from SOX2-POU5F1 to ZIC2-OTX2 in the pluripotent stem cells representing pre-implantation and post-implantation stages.2017

    • Author(s)
      Kondoh H, Matsuda K, Oki S, Shigenobu S.
    • Organizer
      ConBio2017
  • [Presentation] エピブラスト幹細胞株から樹立された領域特性をもつ神経幹細胞株の解析2017

    • Author(s)
      中村香絵、Boitet C、吉氷康矢、飯田英明、近藤寿人
    • Organizer
      ConBio2017
  • [Presentation] Foxa2とともにnEGFPを発現するエピブラスト幹細胞を用いた、初期発生過程の研究2017

    • Author(s)
      稲森祥子、石井泰雄、近藤寿人
    • Organizer
      ConBio2017
  • [Presentation] ヘンゼン結節は脊索前板の発生を介して、Otx2を発現するエピブラストに頭部を形成させる2017

    • Author(s)
      吉氷康矢、近藤寿人
    • Organizer
      ConBio2017
  • [Presentation] Sox2の神経系での発現を制御するD1エンハンサーの解析2017

    • Author(s)
      飯田英明、内川昌則、近藤寿人
    • Organizer
      ConBio2017
  • [Presentation] SOX2-dependent determination of tissue identity in the foregut.2017

    • Author(s)
      Teramoto M, Sugawara R, Ishii Y, Kuroiwa A, Kondoh H.
    • Organizer
      ISDB 2017
    • Int'l Joint Research
  • [Presentation] Roles for ZIC2 in the regulation of epiblast stem cells and embryonic stem cells.2017

    • Author(s)
      Kondoh H, Matsuda K, Oki S, Shigenobu S.
    • Organizer
      ISDB 2017
    • Int'l Joint Research
  • [Presentation] Embryonic region-dependent development and interactions of grafted Hensen’s node with host tissues: reconsideration of organizer model.2017

    • Author(s)
      Kondoh H, Yoshihi K.
    • Organizer
      50th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research / Invited
  • [Presentation] Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of “lens transdifferentiation”.2017

    • Author(s)
      Iida H, Ishii Y, Kondoh H.
    • Organizer
      50th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Presentation] Establishment of neural progenitor cells lines with defined regional specificities from EpiSCs.2017

    • Author(s)
      Nakamura K, Boitet C, Satake S, Yoshihi K, Iida H, Ishii Y, Kondoh H.
    • Organizer
      50th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Presentation] Establishment and use of a new epiblast stem cell line marking Foxa2 expression with GFP.2017

    • Author(s)
      Inamori S, Ishii Y, Kondoh H.
    • Organizer
      50th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Presentation] SOX2-dependent determination of tissue identity in the foregut.2017

    • Author(s)
      Teramoto M, Sugawara R, Ishii Y, Kuroiwa A, Kondoh H.
    • Organizer
      50th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Presentation] Functional genomics of peri- and post-implantation stage stem cells2016

    • Author(s)
      Kondoh H, Matsuda K, Mikami, T. Oki S, Shigenobu S.
    • Organizer
      The 39th Annual Meeting of Molecular Biology Society Japan.
  • [Presentation] Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation.2016

    • Author(s)
      Iida T, Ishii Y, Kondoh H.
    • Organizer
      The 39th Annual Meeting of Molecular Biology Society Japan.
  • [Presentation] Functional genomics of peri- and post-implantation stage stem cells.2016

    • Author(s)
      Kondoh, H.
    • Organizer
      IRM Distinguished Lectures, University of Pennsylvania Institute for Regenerative Medicine.
    • Int'l Joint Research / Invited
  • [Presentation] Genome-wide functional interactions of five major transcriptional factors in mouse epiblast stem cells.2016

    • Author(s)
      Kondoh H, Matsuda K, Mikami, T. Oki S, Shigenobu S.
    • Organizer
      Cell Symposia: Transcriptional Regulation in Development and Disease.
    • Int'l Joint Research
  • [Presentation] Simultaneous promotion of neuronal and lens development from chicken embryonic neural retina.2016

    • Author(s)
      Iida H, Ishii Y, Kondoh H.
    • Organizer
      49th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Presentation] Reinvestigation of the developmental potentioal of grafted Hensen’s node.2016

    • Author(s)
      Yoshihi K, Ishii Y. Kondoh H.
    • Organizer
      49th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Presentation] Direct derivation of embryonic neural progenitor cell lines from epiblast stem cells.2016

    • Author(s)
      Nakamura K, Boitet C, Satake S, Yoshihi K, Ishii Y, Kondoh H.
    • Organizer
      49th Annual Meeting of the Japanese society of Developmental Biologists.
    • Int'l Joint Research
  • [Remarks] Laboratory of Developmental Biology 発生生物学研究室

    • URL

      https://www.cc.kyoto-su.ac.jp/~i1659235/HKlab/index.html

  • [Remarks] 再生医療の地図を描くエピブラスト幹細胞

    • URL

      https://www.kyoto-su.ac.jp/faculty/professors/nls/ahcetq00000023w2-att/st_kondo.pdf

  • [Remarks] SOX2に導かれた、発生の遺伝子制御の道

    • URL

      https://www.kyoto-su.ac.jp/graduate/g_ls/kenkyu/kondo.html

  • [Remarks] 教員紹介 近藤寿人

    • URL

      https://www.kyoto-su.ac.jp/graduate/g_ls/kyoin/kondo.html

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Published: 2018-12-17   Modified: 2022-02-22  

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