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Molecular mechanisms of development of the stem cell niche regulating intestinal epithelial dedifferentiation

Research Project

Project/Area Number 24570078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphology/Structure
Research InstitutionNippon Medical School

Principal Investigator

ISHIZUYA-OKA Atsuko  日本医科大学, 医学部, 教授 (50175254)

Co-Investigator(Renkei-kenkyūsha) HASEBE Takashi  日本医科大学, 医学部, 准教授 (70329027)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords小腸 / 幹細胞 / 上皮脱分化 / 甲状腺ホルモン / 変態 / アフリカツメガエル / ニッチ / シグナル伝達経路 / 器官培養 / Wnt
Outline of Final Research Achievements

In the amphibian digestive tract, some of larval epithelial cells dedifferentiate into adult stem cells by the inductive action of thyroid hormone (TH). In the present study, to clarify molecular mechanisms underlying the epithelial dedifferentiation into the stem cells, we performed expression and functional analyses of TH response genes, using the culture system for the Xenopus laevis small intestine. Our results indicate that TH-activated Wnt5a/Ror2 signaling is essential for the larval epithelial dedifferentiation accompanied by changes in cell morphology. In addition, our findings strongly suggest that absorptive epithelial cells expressing Ror2, which are scattered in the larval epithelium, can dedifferentiate into the stem cells. To clarify the origin of the stem cells, we isolated the promoter of Ror2 and started to generate transgenic frogs for lineage analysis of the epithelial cells expressing Ror2.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] A requirement for hedgehog signaling in thyroid hormone-induced postembryonic intestinal remodeling.2015

    • Author(s)
      Wen, L., Hasebe, T., Miller T.C., Ishizuya-Oka, A., Shi Y.-B.
    • Journal Title

      Cell & Bioscience

      Volume: 5 Issue: 1 Pages: 1-12

    • DOI

      10.1186/s13578-015-0004-3

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thyroid hormone-regulated Wnt5a/Ror2 signaling is essential for dedifferentiation of larval epithelial cells into adult stem cells in the Xenopus laevis intestine.2014

    • Author(s)
      Ishizuya-Oka, A., Kajita M., Hasebe, T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 9 Pages: e107611-e107611

    • DOI

      10.1371/journal.pone.0107611

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression profiling of intestinal tissues implicates novel genes and pathways essential for adult stem cell development2013

    • Author(s)
      Sun, G., Heimeier R. A., Fu, L., Hasebe, T., Das, B., Ishizuya-Oka, A., Shi, Y.-B.
    • Journal Title

      Endocrinology

      Volume: 154 Issue: 11 Pages: 4396-4407

    • DOI

      10.1210/en.2013-1432

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Thyroid hormone-induced cell-cell interactions in the development of adult intestinal stem cells2013

    • Author(s)
      Hasebe, T., Liezhen Fu, L., Thomas C. Miller, T. C., Zhang, Y., Shi Y.-B., Ishizuya-Oka., A.
    • Journal Title

      Cell & Bioscience

      Volume: 3 Issue: 1 Pages: 18-18

    • DOI

      10.1186/2045-3701-3-18

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tissue-specific upregulation of MDS/EVI gene transcripts in the intestine by thyroid hormone during Xenopus metamorphosis2013

    • Author(s)
      Miller TC, Sun G, Hasebe T, Fu L, Heimeier RA, Das B, Ishizuya-Oka A, Shi Y-B
    • Journal Title

      PLoS One

      Volume: 8 Issue: 1 Pages: e55585-e55585

    • DOI

      10.1371/journal.pone.0055585

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of intestinal stem cell niche during amphibian metamorphosis2013

    • Author(s)
      Ishizuya-Oka A, Hasebe T
    • Journal Title

      Current Topics in Developmental Biology

      Volume: 103 Pages: 305-327

    • DOI

      10.1016/b978-0-12-385979-2.00011-3

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Notch signaling-dependent gene expression of Hairy1 and Hairy2b during adult stem cell development in the Xenopus laevis intestine2014

    • Author(s)
      Hasebe, T., Kajita, M., Ishizuya-Oka, A.
    • Organizer
      The 8th biennial conference of the ISAREN
    • Place of Presentation
      基礎生物学研究所(岡崎)
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] アフリカツメガエル変態期の消化管再構築におけるJagged 1とJagged 2の発現解析2014

    • Author(s)
      関本篤人、福永悦也、梶田満子、長谷部孝、岡敦子
    • Organizer
      第85回日本動物学会大会
    • Place of Presentation
      東北大学(仙台)
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] アフリカツメガエル小腸上皮の脱分化機構:Wnt5a/Ror2シグナルの関与

    • Author(s)
      岡 敦子、長谷部 孝
    • Organizer
      第84回日本動物学会大会
    • Place of Presentation
      岡山大学(岡山)
    • Related Report
      2013 Research-status Report
  • [Presentation] アフリカツメガエル変態期の小腸におけるHairy-1とHairy-2bの発現はNotchシグナル依存的である

    • Author(s)
      長谷部 孝、岡 敦子
    • Organizer
      第84回日本動物学会大会
    • Place of Presentation
      岡山大学(岡山)
    • Related Report
      2013 Research-status Report
  • [Presentation] アンドロゲンとその受容体はツチガエルの性を決める?

    • Author(s)
      児玉 万穂、藤井 淳、松尾 安希、長谷部 孝、岡 敦子、中村 正久
    • Organizer
      第84回日本動物学会大会
    • Place of Presentation
      岡山大学(岡山)
    • Related Report
      2013 Research-status Report
  • [Presentation] 甲状腺ホルモンが制御する小腸上皮幹細胞の発生:変態現象をモデルとした進化発生学的考察

    • Author(s)
      岡 敦子
    • Organizer
      第56回日本甲状腺学会学術集会
    • Place of Presentation
      和歌山県民文化会館
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] トランスジェニックカエルは2度輝く:変態期の消化管上皮幹細胞の起源と発生のメカニズム

    • Author(s)
      長谷部孝、岡敦子
    • Organizer
      第83回日本動物学会大会
    • Place of Presentation
      大阪大学(大阪)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] アフリカツメガエル変態期の消化管再構築におけるhairy-1およびhairy-2bの発現解析

    • Author(s)
      長谷部孝、梶田満子、岡敦子
    • Organizer
      第83回日本動物学会大会
    • Place of Presentation
      大阪大学(大阪)
    • Related Report
      2012 Research-status Report
  • [Book] Cell and Molecular Biology and Imaging of Stem Cells: 6. Regulation of adult intestinal stem cells through thyroid hormone-induced tissue interactions during amphibian metamorphosis.2014

    • Author(s)
      Schatten H.編 Ishizuya-Oka, A. 他
    • Total Pages
      292
    • Publisher
      John Wiley & Sons, Inc.
    • Related Report
      2014 Annual Research Report
  • [Remarks] 日本医科大学知的財産推進センター

    • URL

      http://tlo.nms.ac.jp/researcher/762.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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