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2018 年度 実績報告書

ヒトiPS肝芽再構成系を用いた血液細胞との相互作用により肝細胞分化制御機構の解明

研究課題

研究課題/領域番号 18F18101
研究機関横浜市立大学

研究代表者

谷口 英樹  横浜市立大学, 医学研究科, 教授 (70292555)

研究分担者 NIE YUNZHONG  横浜市立大学, 医学部, 外国人特別研究員
研究期間 (年度) 2018-04-25 – 2020-03-31
キーワードhiPSC / Organoid / Hepatocyte / Hematopoietic cells / Cell-cell interactions / Liver disease / Liver organogenesis / CD14
研究実績の概要

In this study, we are going to understand how the dynamic interactions between hematopoietic and hepatic cells regulate liver development, and to generate the functional liver organoid that can be used for liver disease study and model. For this purpose, we try to establish an organoid to recapitulate hematopoietic-hepatic interactions during early liver organogenesis. In the last year, we successfully established a hematopoietic-hepatic organoid, and found that hematopoietic cells could improve hepatic maturation and hepatic microenvironment helped to maintain the viability of hematopoietic cells. Moreover, we identified that CD14+ cells were that effective hematopoietic population, and noticed that hepatic lineages derived signals could promote the differentiation of CD14+ cells.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

With the established hematopoietic-hepatic organoid, we recapitulated the hematopoietic-hepatic interaction during organoid development, and we figured out the effective hematopoietic population that can promote hepatocyte maturation. These findings confirmed the value of this organoid system in further revealing the dynamic interactions between hematopoietic-hepatic cells in human being. Therefore, this plan is expected to progress smoothly.

今後の研究の推進方策

In this year, we are going to further explore the underlying mechanisms of the dynamic interactions by comprehensively analyzing hepatic cells and hematopoietic cells with RNA sequencing and bioinformatics analysis, and try to in vivo verify symbiotic relationship between liver organogenesis and hematopoiesis with animal models. Moreover, we also want to characterize the function of hematopoietic-liver organoid in liver injury mice. Finally, we will summarize the results and publish related papers.

  • 研究成果

    (3件)

すべて 2019 2018

すべて 雑誌論文 (1件) (うち国際共著 1件、 査読あり 1件、 オープンアクセス 1件) 学会発表 (2件) (うち国際学会 1件)

  • [雑誌論文] Recapitulation of hepatitis B virus?host interactions in liver organoids from human induced pluripotent stem cells2018

    • 著者名/発表者名
      Nie Yun-Zhong、Zheng Yun-Wen、Miyakawa Kei、Murata Soichiro、Zhang Ran-Ran、Sekine Keisuke、Ueno Yasuharu、Takebe Takanori、Wakita Takaji、Ryo Akihide、Taniguchi Hideki
    • 雑誌名

      EBioMedicine

      巻: 35 ページ: 114~123

    • DOI

      10.1016/j.ebiom.2018.08.014

    • 査読あり / オープンアクセス / 国際共著
  • [学会発表] Modeling hepatitis B virus-host interactions in hiPSC derived liver organoids2019

    • 著者名/発表者名
      Yun-Zhong Nie
    • 学会等名
      日本再生医療学会総会
  • [学会発表] RESCUE OF MOUSE ACUTE LIVER FAILURE BY HUMAN LIVER ORGANOIDS GENERATED WITH SINGLE DONOR DERIVED MULTIPLE CELLS2018

    • 著者名/発表者名
      Yun-Zhong Nie
    • 学会等名
      International Society for Stem Cell Research
    • 国際学会

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公開日: 2019-12-27  

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