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Dynamics of hepatocyte and progenitor cells during pregnancy

Research Project

Project/Area Number 17K19697
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Surgery of the organs maintaining homeostasis and related fields
Research InstitutionKyoto University

Principal Investigator

Toyoshima Fumiko  京都大学, ウイルス・再生医科学研究所, 教授 (40397576)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords妊娠 / 肝蔵 / 増殖 / 肝臓 / 増殖・分化 / 細胞増殖・分化 / 発生・分化 / 細胞・組織 / 生殖
Outline of Final Research Achievements

In mammals, maternal environments influence embryonic development. During pregnancy, maternal organs change their size and functions to accommodate fetal growth. The organs that are expanded in the size during pregnancy include maternal liver, which would be important for metabolic change in gestation period. However, little is known how liver parenchymal and nonparenchymal cells are regulated during pregnancy. In this project, we found in mice that hepatocytes and bile duct epithelial cells proliferate at early stage of pregnancy. Cell-trace assay by labeling the hepatocyte progenitor cells and bile duct epithelial cells show that these cells divide and proliferate stochastically during pregnancy. We are now investigating the changes of gene expression profiles in both hepatocytes and bile-duct epithelial cells during pregnancy to identify the responsible genes for their proliferation.

Academic Significance and Societal Importance of the Research Achievements

現行の生殖研究は、卵子・精子の質やiPS細胞から生殖細胞の作出など、配偶子側からの解析が中心であるが、配偶子から個体を得るには、胎児発生の場としての母体の機能を細胞レベルで明らかにする必要がある。妊娠期には、母体の代謝機能が大きく変化する。肝臓は代謝機能を担う第一の臓器であるため、妊娠期における肝蔵の細胞ダイナミクスの解明は、安心・安全な妊娠・出産の実現に重要である。本研究により、肝細胞・胆管上皮細胞が妊娠期に増殖亢進することが明らかとなった。今後、この増殖亢進を担う遺伝子やシグナル伝達を明らかにすることにより、妊娠における代謝機能の変化を細胞・遺伝子レベルで解明することができる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2018 2017

All Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] 肝細胞の時空間依存的細胞分裂による妊娠期母体肝細胞再編成機構の解析2018

    • Author(s)
      上月智司、豊島文子
    • Organizer
      第25回肝細胞研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝臓内ゾーン依存的な妊娠期母体肝細胞再編成機構の解析2018

    • Author(s)
      上月智司、豊島文子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanisms of Hepatocyte Division During Pregnancy2018

    • Author(s)
      Elizabeth Shimoura, Riki Ishibashi, Sachiko Kamakura, Satoshi Kozuki, Hideki Sumimoto, Fumiko Toyoshima
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Zonation-dependent hepatocytes dynamics during pregnancy.2018

    • Author(s)
      Satoshi Kozuki, Fumiko Toyoshima
    • Organizer
      25th East Asia Joint Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dynamics of liver stem/progenitor cells during pregnancy2017

    • Author(s)
      上月智司、豊島文子
    • Organizer
      第15回幹細胞シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 妊娠期における、肝細胞・肝幹細胞の時空間依存的細胞分裂による肝細胞再編成機構の解析2017

    • Author(s)
      上月智司、豊島文子
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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