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Functional analysis of liver stem/progenitor cell in liver regeneration and carcinogenesis

Research Project

Project/Area Number 25670187
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionResearch Institute, International Medical Center of Japan (2014)
The University of Tokyo (2013)

Principal Investigator

TANAKA Minoru  独立行政法人国立国際医療研究センター, その他部局等, 室長 (80321909)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords幹細胞 / 再生 / 肝細胞 / 胆管上皮細胞 / 前駆細胞 / 肝障害 / 肝再生 / 細胞運命 / 肝幹/前駆細胞 / 肝癌幹細胞
Outline of Final Research Achievements

Hepatic oval cell is observed in chronic liver injury models of rodents and considered as liver stem/progenitor cell, which is capable of differentiating into biliary epithelial cells and hepatocytes. However, the contribution of hepatic oval cell to liver regeneration remains unclear. Because we have previously reported that Trop2 is a specific marker gene for mouse hepatic oval cells, we generated a genetically engineered mouse in which the Cre-recombinase was knocked in to the Trop2 locus for lineage-tracing analysis. As a result, most of hepatic oval cells formed pseudo-biliary ducts and rarely produced hepatocytes in the DDC-injured liver, indicating that hepatic oval cells don’t mainly contribute to the supply of hepatocytes at least in this liver injury model.

Report

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

    (21 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (9 results) (of which Invited: 3 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Oncostatin M maintains the hematopoietic microenvironment in the bone marrow by affecting adipogenesis and osteoblastogenesis.2014

    • Author(s)
      Sato F, Miyaoka Y, Miyajima A and Tanaka M.
    • Journal Title

      PLoS One 2014 Dec 31

      Volume: 9(12) Issue: 12 Pages: e116209-e116209

    • DOI

      10.1371/journal.pone.0116209

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Semaphorin 3E secreted by damaged hepatocytes regulates the sinusoidal regeneration and liver fibrosis during liver regeneration.2014

    • Author(s)
      Yagai T, Miyajima A, Tanaka M
    • Journal Title

      American Journal of Pathology

      Volume: 184 Issue: 8 Pages: 2250-2259

    • DOI

      10.1016/j.ajpath.2014.04.018

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming.2014

    • Author(s)
      Atsushi Miyajima, Minoru Tanaka, and Tohru Itoh
    • Journal Title

      Cell Stem Cell

      Volume: 14 Issue: 5 Pages: 561-574

    • DOI

      10.1016/j.stem.2014.04.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel function of Oncostatin M as a potent tumor-promoting agent in lung.2014

    • Author(s)
      Lauber S, Wong S, Cutz JC, Tanaka M, Barra N, Lhoták S, Ashkar A, Richards CD.
    • Journal Title

      Int J Cancer

      Volume: 136 Issue: 4 Pages: 831-43

    • DOI

      10.1002/ijc.29055

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of OSMRb exacerbates high-fat diet-induced obesity and related metabolic disorders in mice.2014

    • Author(s)
      Komori T, Tanaka M, Semba M, Miyajima A, and Morikawa Y.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Issue: 20 Pages: 13821-13837

    • DOI

      10.1074/jbc.m113.542399

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deficiency of OSMRβ Exacerbates High-Fat Diet-Induced Obesity and Related Metabolic Disorders in Mice2014

    • Author(s)
      Komori T, Tanaka M, Senba E, Miyajima A, Morikawa Y.
    • Journal Title

      J Biol Chem

      Volume: -

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nrf2 enhances cholangiocyte expansion in Pten-deficient livers.2014

    • Author(s)
      Taguchi K, Hirano I, Itoh T, Tanaka M, Miyajima A, Suzuki A, Motohashi H, and Yamamoto M.
    • Journal Title

      Mol. Cell. Biol.

      Volume: 34 Issue: 5 Pages: 900-913

    • DOI

      10.1128/mcb.01384-13

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lack of oncostatin M receptor β leads to adipose tissue inflammation and insulin resistance by switching macrophage phenotype2013

    • Author(s)
      Komori T, Tanaka M, Senba E, Miyajima A, Morikawa Y
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 30 Pages: 21861-21875

    • DOI

      10.1074/jbc.m113.461905

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nephronectin is upregulated in acute and chronic hepatitis and aggravates liver injury by recruiting CD4 positive cells2013

    • Author(s)
      Inagaki F., Tanaka M., Inagaki N., Yagai T., Sato Y., Sekiguchi K., Oyaizu N., Kokudo N., and Miyajima A
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 430 Issue: 2 Pages: 751-756

    • DOI

      10.1016/j.bbrc.2012.11.076

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] TROP2を指標としたBiliary Tree Stem/Progenitor Cellの単離および培養系の構築2014

    • Author(s)
      松井理司、田中稔、宮島篤
    • Organizer
      第37回日本分子生物学会
    • 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] Lutheranの発現を指標とした肝幹/前駆細胞の性状解析2014

    • Author(s)
      三浦泰史、田中稔、吉川大和、合田亘人、宮島篤
    • Organizer
      第37回日本分子生物学会
    • 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] 細胞死から見た肝臓の再生と線維化の制御機構の解明2014

    • Author(s)
      田中稔
    • Organizer
      新学術領域「ダイイングコード」キックオフシンポジウム
    • Place of Presentation
      東京大学 山上会館
    • Year and Date
      2014-11-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞死から見た肝臓の再生と線維化のメカニズム2014

    • Author(s)
      田中稔
    • Organizer
      第23回日本Cell Death学会
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2014-07-18 – 2014-07-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Lutheranの発現を指標とした肝幹/前駆細胞の性状解析2014

    • Author(s)
      三浦泰史、田中稔、吉川大和、合田亘人、宮島篤
    • Organizer
      第21回肝細胞研究会
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2014-06-27 – 2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 胆管傷害および胆管癌におけるsterile alpha motif domain containing 5の発現解析2014

    • Author(s)
      谷貝知樹、松井理司、原田憲一、稲垣冬樹、西條栄子、中沼安二、宮島篤、田中稔
    • Organizer
      第21回肝細胞研究会
    • Place of Presentation
      東京医科歯科大学
    • Year and Date
      2014-06-27 – 2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Oncostatin M regulates the crosstalk between insulin resistance and liver fibrosis by switching the M1/M2 activation of macrophage.2013

    • Author(s)
      Minoru Tanaka, Tadasuke Komori, Michitaka Matsuda, Yoshihiro Morikawa, Atsushi Miyajima
    • Organizer
      International Symposium on Transcription and Metabolism.
    • Place of Presentation
      兵庫県・淡路島
    • Related Report
      2013 Research-status Report
  • [Presentation] P75NTR-positive mesenchymal cells contribute to erythropoiesis in both fetal and adult liver by expressing erythropoietin.2013

    • Author(s)
      Minoru Tanaka, Marika Motomura, Yoshiko Kamiya and Atsushi Miyajima
    • Organizer
      JAPAN LIVER CELL WEEK (第20回肝細胞研究会)
    • Place of Presentation
      大阪国際会議場(グランキューブ大阪)
    • Related Report
      2013 Research-status Report
  • [Presentation] 肝細胞死から見た肝障害後の再生および線維化の制御機構2013

    • Author(s)
      田中稔、谷貝知樹、宮島篤
    • Organizer
      第86回日本生化学会シンポジウム「多様な細胞死を起点とする生体制御ネットワーク」
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 臨床免疫・アレルギー科2015

    • Author(s)
      田中稔
    • Publisher
      科学評論社
    • Related Report
      2014 Annual Research Report
  • [Book] サイトカイン・増殖因子 キーワード辞典2015

    • Author(s)
      田中稔
    • Total Pages
      420
    • Publisher
      羊土社
    • Related Report
      2014 Annual Research Report
  • [Remarks] 国立国際医療研究センター研究所 組織再生医学研究部

    • URL

      http://ncgm-regenerative-medicine.org/

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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