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Multi-potential epithelial cells linked with branching airway structure.

Research Project

Project/Area Number 26713029
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Morimoto Mitsuru  国立研究開発法人理化学研究所, 多細胞システム形成研究センター, チームリーダー (70544344)

Co-Investigator(Renkei-kenkyūsha) NOGUCHI MASAFUMI  国立研究開発法人理化学研究所, 多細胞システム研究センター, 研究員 (50714870)
SUMIYAMA KENTA  国立研究開発法人理化学研究所, 生命システム研究センター, ユニットリーダー (00370114)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2016: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2015: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords呼吸器上皮 / 組織幹細胞 / 枝分かれ構造 / Notchシグナル / 気道上皮細胞 / 発生学 / 神経内分泌細胞 / 発生・分化 / 細胞・組織 / シグナル伝達 / 遺伝子 / 呼吸器 / 発生 / 幹細胞
Outline of Final Research Achievements

In this study, we aim to elucidate the developmental process of the stem cell - niche complex tissue "NEB" at the bronchial branch point, and elucidate the molecular dynamics of the tissue stem cells contained in NEB. Our new transgenic mice demonstrated that Notch-activated cells surrounding NE cells do not reduce the number of NE cells by cell-cell contact. On the other hand, mouse genetic analysis revealed that Notch-Hes1 cascade coordinates the number of NE cells by supressing the NE cell fate in the cell autonomous fashion in the early stages of development. Furthermore, we succeeded in 4D live imaging of developing NE cells using multiphoton-microscopy in being the first in the world, and illustrated that solitary NE cells in the early fetal lung directionaly migrate to the bronchial branch point to form NEBs. Finally, we established the technique to isolate NE cells from fetal lung and conducted a micro array analysis.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (28 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Int'l Joint Research: 8 results,  Invited: 16 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] コロンビア大学医学部(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] 国立台湾大学病院(台湾)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity.2016

    • Author(s)
      Tsao P*, Matsuoka C, Wei SC, Sato A, Sato S, Chena HK, Ling TY, Mori M, Cardoso WV, Morimoto M*.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 113 Issue: 29 Pages: 8242-8247

    • DOI

      10.1073/pnas.1511236113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 臓器の多彩な細胞パターン形成を指揮するNotch2016

    • Author(s)
      野口雅史、森本充
    • Journal Title

      実験医学;Notchシグナルの新世紀

      Volume: 34 Pages: 409-415

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Directed migration of pulmonary neuroendocrine cells toward airway branches organizes the stereotypic location of neuroepithelial bodies.2015

    • Author(s)
      Noguchi, M., Sumiyama, K., Morimoto M.
    • Journal Title

      Cell Reports

      Volume: 13 Issue: 12 Pages: 2679-86

    • DOI

      10.1016/j.celrep.2015.11.058

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A promoter-level mammalian expression atlas.2014

    • Author(s)
      Forrest, A.R.R., Kawaji, H., Rehli, M., Baillie, J.K, de Hoon, M.J.L., Haberle, V., Lassmann, T., Kulakovskiy, I.V., Lizio, M., Itoh, M., Andersson, R., Mungall, C. J.,et al.
    • Journal Title

      Nature

      Volume: 507 Issue: 7493 Pages: 462-470

    • DOI

      10.1038/nature13182

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 多様な気道上皮細胞とNotchシグナルによる分化制御2014

    • Author(s)
      森本充
    • Journal Title

      呼吸と循環

      Volume: 62 Pages: 689-696

    • NAID

      40020132545

    • Related Report
      2014 Annual Research Report
  • [Presentation] 幹細胞ヒエラルキーとその形成機序.2017

    • Author(s)
      森本充
    • Organizer
      千里ライフサイエンスセミナー 「組織を支える幹細胞と微小環境(ニッチ)」.
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府豊中市)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 2光子レーザー顕微鏡が可能にした呼吸器の動的発生の発見と1細胞レベルの形態定量.2017

    • Author(s)
      森本充
    • Organizer
      第9回呼吸機能イメージング研究会学術集会
    • Place of Presentation
      京都大学(京都府京都市)
    • Year and Date
      2017-01-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Alternative cell fate selection and following directed cell migration coordinate epithelial pattern of branching airways2017

    • Author(s)
      森本充
    • Organizer
      第50回日本発生生物学学会シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Alternative cell fate selection and following directed cell migration coordinate epithelial pattern of branching airways2017

    • Author(s)
      森本充
    • Organizer
      The 8th TAKAO International Symposium on Molecular Mechanism of Cardiopulmonary Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Wnt5a-Ror2シグナルは気管の間充織細胞の極性を同調させ管腔の長さを制御する2017

    • Author(s)
      森本充、岸本圭史
    • Organizer
      第40回日本分子生物学会ワークショップ
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Notch mediated-alternative cell fate selection and following directed cell migration coordinate epithelial pattern of branching airways.2016

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      第39回日本分子生物学会年会ワークショップ
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Alternative cell fate selection and following directed cell migration coordinate epithelial pattern of branching airways.2016

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      Malaysia Tissue Engineering and Regenerative Medicine 2016
    • Place of Presentation
      the light hotel(マレーシア ペナン島)
    • Year and Date
      2016-11-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 呼吸器の発生と再生を幹細胞で繋げる.2016

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      日本肺サーファクタント・界面医学会第52回学術研究会
    • Place of Presentation
      金沢医科大学(石川県金沢市)
    • Year and Date
      2016-10-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Oriented mesenchymal cells drive tracheal tubulogenesis2016

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      LUNG REPAIR AND REGENERATION CONSORTIUM, 2016 ANNUAL MEETING
    • Place of Presentation
      Bethesda Marriott Suites(米国ワシントンDC)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 3D mapping and 4D imaging unveiled the size and positional regulation of developing neuroepithelial bodies following airway branching morphogenesis.2016

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      FASEB Science Research Conferences
    • Place of Presentation
      Saxtons River(米国バーモント州)
    • Year and Date
      2016-08-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Alternative cell fate selection and following directed cell migration coordinate epithelial pattern of branching airways.2016

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      第14回幹細胞シンポジウム
    • Place of Presentation
      淡路夢舞台(兵庫県淡路島)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 呼吸器上皮の発生・再生のロジック2015

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      第23回呼吸器疾患・感染症研究会
    • Place of Presentation
      千里阪急ホテル(大阪府大阪市)
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] A stepwise process regulating the neuroendocrine cell population and localization at the bifurcation points of the branching bronchioles.2015

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      Stem Cells and Cell Therapies in Lung Biology and Diseases Conference
    • Place of Presentation
      University of Vermont(米国バーモント州)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A non-proliferating tissue enlargement controlling the trachea tubulogenesis.2015

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      Keystone Symposia; Endoderm Lineages in Development and Disease
    • Place of Presentation
      Keystone, Colorado
    • Year and Date
      2015-02-10
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Notch signaling contributes to population and regional regulations of the airway epithelial stem and differentiated cells2014

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      第87回日本生化学会大会シンポジウム
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Notch signaling contributes to population and regional regulations of the airway epithelial stem and differentiated cells.2014

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      第47回発生生物学会年会シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-28
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Notch signaling integrates postnatal morphogenesis of the distal most bronchiole and alveoli via epithelial-mesenchymal interaction.2014

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      呼吸器学会学術講演会
    • Place of Presentation
      Osaka International Convention Center
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Book] Building Functional Internal Organs from a Naive Endodermal Sheet, New Principles in Developmental Processes, Part I-52014

    • Author(s)
      Mitsuru Morimoto
    • Total Pages
      316
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究室HP

    • URL

      http://www.cdb.riken.jp/lungdev/index-en.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] CDBニュース 肺の神経内分泌細胞は気管支の“股”に集まる

    • URL

      http://www.cdb.riken.jp/news/2015/researches/1221_9279.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 理化学研究所プレスリリース(研究成果) 肺の細胞が自ら歩いて集まる様子を撮影

    • URL

      http://www.riken.jp/pr/press/2015/20151218_1/

    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2022-02-16  

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