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下垂体未分化細胞の分化転換における組織特異的転写因子PROP1の機能解析

Research Project

Project/Area Number 12J10032
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionMeiji University

Principal Investigator

吉田 彩舟  明治大学, 農学研究科 生命科学専攻, 特別研究員(DC1)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2014: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2013: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2012: ¥900,000 (Direct Cost: ¥900,000)
Keywords下垂体 / 幹・前駆細胞 / Niche / 発生・分化 / ephrin/Eph signal / 組織特異的転写因子 / 標的遺伝子 / ephrin/Eph Receptor signal / 標的遺伝子探索 / 相互作用因子探索
Outline of Annual Research Achievements

本研究は下垂体特異的転写因子PROP1の幹・前駆細胞における機能解析ならびに、それら幹・前駆細胞を支持する微小環境(Niche)の解析を目的としている。具体的には 1. ChIP-Seq法を用いたPROP1の標的遺伝子探索、さらに、2. Nicheで特異的に機能するシグナル分子の同定と機能解析を行う。本年度の研究成果は以下の通りである。

1. PROP1の標的遺伝子探索:今年度までに抗体の準備ならびに実験系の構築、ならびにChIP-Seq解析用のサンプル準備が終了した。現在、次世代シークエンサーを用いた委託解析を予定している。

2. Nicheを制御するシグナル分子の同定と機能解析:本年度は前年度に見出した、下垂体幹・前駆細胞Nicheで発現するシグナル伝達分子ephrin-B2/EphB3の活性化機序に関して解析を行った。組織化学的解析から、成体下垂体におけるephrin-B2とEphB3の存在様式は不活性型のCis-interactionを形成していることを確認した。一方で、分化の盛んな出生直後では、EphB3とのCis-interactionが解除され、ニッチ周囲に存在するACTH産生細胞が発現するEphB2と活性型のTrans-interactionを形成していることを見出した。これらの知見から、下垂体の幹・前駆細胞ニッチではCis-interactionを利用したニッチ内部における第1次的(抑制的)な制御と、周囲の分化細胞を利用した第2次的(活性的)な制御により、幹・前駆細胞の幹細胞性維持と、分化転換におけるニッチからの離脱が制御されているという、新たなモデルが示唆された。本研究内容の一部は筆頭著者としてCell Tissue Res.に投稿し、受理された。現在、さらに2報の論文として取りまとめ、投稿準備をしている。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (12 results) (of which Invited: 1 results)

  • [Journal Article] PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development2015

    • Author(s)
      Masashi Higuchi, Takako Kato, Saishu Yoshida, Hiroki Ueharu, Naoto Nishimura, Yukio Kato
    • Journal Title

      Cell Tissue Res.

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localization of juxtacrine factor ephrin-B2 in pituitary stem/progenitor cell niches throughout life.2014

    • Author(s)
      Saishu Yoshida, Takako Kato, Masashi Higuchi, Mo Chen, Hiroki Ueharu, Naoto Nishimura, Yukio Kato
    • Journal Title

      Cell Tissue Res.

      Volume: 359 Issue: 3 Pages: 755-766

    • DOI

      10.1007/s00441-014-2054-y

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proton receptor GPR68 expression in dendritic-cell-like S100β-positive cells of rat anterior pituitary gland: GPR68 induces interleukin-6 gene expression in extracellular acidification2014

    • Author(s)
      Kotaro Horiguchi, Masashi Higuchi, Saishu Yoshida, Takashi Nakakura, Kozue Tateno, Rumi Hasegawa, Shu Takigami, Shunji Ohsako, Takako Kato, Yukio Kato
    • Journal Title

      Cell Tissue Res.

      Volume: 358 Issue: 2 Pages: 515

    • DOI

      10.1007/s00441-014-1958-x

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PRRX1 and PRRX2 distinctively participate in pituitary organogenesis and a cell-supply system.2014

    • Author(s)
      Masashi Higuchi, Saishu Yoshida, Hiroki Ueharu, Mo Chen, Takako Kato, Yukio Kato
    • Journal Title

      Cell and Tissue Research

      Volume: (印刷中) Issue: 1 Pages: 323-335

    • DOI

      10.1007/s00441-014-1861-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular Cloning of Rat and Porcine Retina-Derived POU Domain Factor 1 (POU6F2) from Pituitary cDNA Library.2014

    • Author(s)
      Saishu Yoshida, Hiroki Ueharu, Masashi Higuchi, Kotaro Horiguchi, Naoto Nishihara, Shiori Shibuya, Hideo Mitsuishi, Takako Kato and Yukio Kato
    • Journal Title

      Journal of Reproduction and Development

      Volume: (印刷中)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of Murine Pituitary-Derived Cell Lines, Tpit/F1, Tpit/E and TtT/GF.2014

    • Author(s)
      Saishu Yoshida, Masashi Higuchi, Hiroki Ueharu, Naoto Nishimura, Mitsuyoshi Tsuda, Hideji Yako, Mo Chen, Hideo Mitsuishi, Yoshiya Sano, Takako Kato, Yukio Kato.
    • Journal Title

      Journal of Reproduction and Development

      Volume: (印刷中)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GFP-expressing S100β-positive cells of the rat anterior pituitary differentiate into hormone-producing cells.2014

    • Author(s)
      Masashi Higuchi, Naoko Kanno, Saishu Yoshida, Hiroki Ueharu, Mo Chen, Hideji Yako, Shioh Shibuya, Masayo Sekita, Mitsuyoshi Tsuda, Hideo Mitsuishi, Naoto Nishimura, Takako Kato, Yukio Kato.
    • Journal Title

      Cell and Tissue Research

      Volume: (印刷中)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of dendritic-cell-like S100β-positive cells in rat anterior pituitary gland.2014

    • Author(s)
      Kotaro Horiguchi, Ken Fujiwara, Saishu Yoshida, Masashi Higuchi, Takehiro Tsukada, Naoko Kanno, Takashi Yashiro, Kozue Tateno, Shunji Osako, Takako Kato, Yukio Kato
    • Journal Title

      Cell and Tissue Research

      Volume: (印刷中) Issue: 1 Pages: 301-308

    • DOI

      10.1007/s00441-014-1817-9

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kruppel-Like Factor6, KLF6, Is Expressed in the Rat Pituitary Stem/Progenitor Cells and Regulates PRRX2 Gene.2014

    • Author(s)
      Hiroki Ueharu, Masashi Higuchi, Naoto Nishiura, Saishu Yoshida, Shiori Shibuya, Kenta Sensui, Takako Kato, Yukio Kato.
    • Journal Title

      Journal of Reproduction and Development

      Volume: (印刷中)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of chemokine CXCL10 in dendritic-cell-like S 100β-positive cells in rat anterior pituitary gland.2014

    • Author(s)
      Kotaro Horiguchi, Ken Fujiwara, Masashi Higuchi, Saishu Yoshida, Takehiro Tsukada, Hiroki Ueharu, Mo Chen, Rumi Hasegawa, Shu Takigami, Shunji Ohsako, Takashi Yashiro, Takako Kato, Yukio Kato.
    • Journal Title

      Cell and Tissue Research

      Volume: (印刷中)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid transition of NESTIN-expressing dividing cells from PROP1-positive to PIT1-positive advances prenatal pituitary development.2013

    • Author(s)
      Saishu Yoshida, Takako Kato, Masashi Higuchi, Hideji Yako, Mo Chen, Naoko Kanno, Hiroki Ueharu, Yukio Kato
    • Journal Title

      Journal of Neuroendocrinolog

      Volume: 25 Pages: 779-791

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coxsackievirus and adenovirus receptor-positive cells compose the putative stem/progenitor cellniches in the marginal cell layer and parenchyma of the ratanterior pituitary.2013

    • Author(s)
      Mo Chen, Takako Kato, Masashi Higuchi, Saishu Yoshida, Hideji Yako, Naoko Kanno, Yukio Kato
    • Journal Title

      Cell and Tissue Research

      Volume: 354 Pages: 823-836

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-dimensional studies of Prop1-expressing cells in the rat pituitary just before birth.2013

    • Author(s)
      Hideji Yako, Takako Kato, Saishu Yoshida, Masashi Higuchi, Mo Chen, Naoko Kanno, Hiroki Ueharu, Yukio Kato.
    • Journal Title

      Cell and Tissue Research.

      Volume: 354 Pages: 837-847

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of a pituitary-tumor-derived cell line, TtT/GF, that expresses Hoechst efflux ABC transporter subfamily G2 and stem cell antigen 1.2013

    • Author(s)
      Hideo Mitsuishi, Takako Kato, Mo Chen, Li-yi Cai, Hideji Yako, Masashi Higuchi, Saishu Yoshida, Naoko Kanno, Hiroki Ueharu, Yukio Kato.
    • Journal Title

      Cell and Tissue Research

      Volume: 354 Pages: 563-572

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of human herpesviruses (HHVs) in semen of human male infertile patients.2013

    • Author(s)
      Mo Chen, li-yi Cai, Naoko Kanno, Takako Kato, Lu Jinxing, Jin Fan, Wang Honghua, Masayo Sekita, Masashi Higuchi, Saishu Yoshida, Hideji Yako, Hiroki Ueharu, Izumi Shun-Ichiro, Yukio Kato.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 59 Pages: 457-462

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temporospatial gene expression of Prxl and Prx2 1S involved in morphogenesis of cranial placode-derived tissues through epithelio-mesenchymal interaction during rat embryogenesis2013

    • Author(s)
      Masashi Higuchi, Takako Kato, MoChen, Hideji Yako, Saishu Yoshid, Naoko Kanno, Yukio Kato
    • Journal Title

      Cell and Tissue Research

      Volume: (in press) Issue: 1 Pages: 27-40

    • DOI

      10.1007/s00441-013-1632-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 下垂体の組織幹・前駆細胞で機能する組織特異的転写因子PROP12012

    • Author(s)
      吉田彩舟、加藤たか子、加藤幸雄
    • Journal Title

      明治大学研究報告

      Volume: 74 Pages: 79-87

    • NAID

      40019657925

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Paired-related homeodomain proteins Prxl and Prx2 are expressed in embryonic pituitary stem/progenitor cells and may be involved in the early stage of pituitary differentiation.2012

    • Author(s)
      Susa T, Kato T, Yoshida S, Yako M, HIguchi M, Kato Y.
    • Journal Title

      Journal of Neuroendocrinology

      Volume: 24 Pages: 1201-1212

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 下垂体幹・前駆細胞で機能する細胞接触型シグナル分子ephrin/Ephの解析2014

    • Author(s)
      吉田彩舟、加藤たか子、樋口雅司、上春浩貴、河合航平、西村直人、加藤幸雄
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 下垂体幹・前駆細胞ニッチに存在するephrin/Ephの同定2014

    • Author(s)
      吉田彩舟、加藤たか子、樋口雅司、上春浩貴、河合航平、加藤幸雄
    • Organizer
      第41回日本神経内分泌学会
    • Place of Presentation
      都道府県会館
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Presence of the juxtacrine factor EphrinB2 in a rat pituitary stem/progenitor cell niche2014

    • Author(s)
      Saishu Yoshida, Kouhei Kawai, Takako Kato, Yukio Kato
    • Organizer
      World Congress of Reproductive Biology 2014
    • Place of Presentation
      Edinburgh International Conference Centre (Edinburgh, Scotland)
    • Year and Date
      2014-09-02 – 2014-09-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 下垂体幹・前駆細胞ニッチにおける ephrin/Eph シグナル分子の同定2014

    • Author(s)
      吉田彩舟、加藤たか子、樋口雅司、陳默、上春浩貴、西村直人、 加藤幸雄
    • Organizer
      第29回 日本下垂体研究会
    • Place of Presentation
      八王子セミナーハウス
    • Year and Date
      2014-08-08 – 2014-08-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 下垂体幹細胞マーカーと膜局在分子による幹・前駆細胞ニッチの解析2014

    • Author(s)
      吉田彩舟、加藤たか子、加藤幸雄
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2014-04-24 – 2014-04-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 下垂体幹・前駆細胞のNicheを制御する細胞間シグナル分子EphrinB2の局在解析2013

    • Author(s)
      吉田彩舟
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      兵庫県
    • Year and Date
      2013-12-04
    • Related Report
      2013 Annual Research Report
  • [Presentation] 下垂体幹・前駆細胞で機能するEphrinシグナル分子の探索2013

    • Author(s)
      吉田彩舟
    • Organizer
      第28回日本下垂体研究会学術集会
    • Place of Presentation
      岩手県
    • Year and Date
      2013-08-07
    • Related Report
      2013 Annual Research Report
  • [Presentation] Characterization of highly trypsin-resistant cells from the adult anterior pituitary.2013

    • Author(s)
      Saishu Yoshida
    • Organizer
      The 95th Endoerine Society Meeting
    • Place of Presentation
      San Francisco, U.S.A
    • Year and Date
      2013-06-17
    • Related Report
      2013 Annual Research Report
  • [Presentation] 下垂体発生過程における幹・未分化細胞の増殖とNESTINの関係2013

    • Author(s)
      吉田彩舟
    • Organizer
      第116回日本畜産学会
    • Place of Presentation
      安田女子大学(広島県)
    • Year and Date
      2013-03-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] 下垂体発生過程におけるNESTIN陽性細胞の局在解析2012

    • Author(s)
      吉田彩舟
    • Organizer
      第39回日本神経内分泌学会学術集会
    • Place of Presentation
      北九州国際会議場(福岡県)
    • Year and Date
      2012-09-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] 下垂体幹・未分化細胞に発現する転写因子PROPlならびにPRXl・PRX2は下垂体の機能形成に関与する2012

    • Author(s)
      吉田彩舟
    • Organizer
      第105回 日本繁殖生物学会大会
    • Place of Presentation
      筑波大学(茨城県)
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] Rapid change of nestin-positive cells in the pituitary during the first postnatal growth wave2012

    • Author(s)
      吉田彩舟
    • Organizer
      The 94th Endocrine Society Meeting
    • Place of Presentation
      Houston
    • Year and Date
      2012-06-25
    • Related Report
      2012 Annual Research Report

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Published: 2013-04-25   Modified: 2024-03-26  

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