ポリコーム群タンパク質を介した肝幹細胞の自己複製制御  [in Japanese] Role of Polycomb group proteins in the hepatic stem cell self-renewal  [in Japanese]

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Author(s)

    • 上野 康晴 UENO Yasuharu
    • 横浜市立大学大学院医学研究科臓器再生医学 Department of Regenerative Medicine, Graduate School of Medicine, Yokohama City University
    • 内藤 貴子 NAITO Takako
    • 横浜市立大学大学院医学研究科臓器再生医学 Department of Regenerative Medicine, Graduate School of Medicine, Yokohama City University
    • 谷口 英樹 TANIGUCHI Hideki
    • 横浜市立大学大学院医学研究科臓器再生医学 Department of Regenerative Medicine, Graduate School of Medicine, Yokohama City University

Abstract

Stem cell are defined as having robust self-renewal and multilineage differentiation potential. It is thought that the self-renewal capability of stem cells can be established when both of the gene clusters involved in maintaining the undifferentiated state and cell differentiation state are expressed neutrally.<br> In present study, we first investigated the role of Polycomb group (PcG) genes in the hepatic stem/progenitor cells. As a result, we revealed that forced expression of Bmi1 promoted the self-renewal of hepatic stem/progenitor cells. The transplantation of Bmi1 introduced cells clonally expanded from single hepatic stem/progenitor cells produced the tumor, which exhibited the histologic features of combined hepatocellular and cholangiocarcinoma. These observations imply that Bmi1 act as a positive regulator of self-renewal capability in hepatic stem cells.<br> Moreover, to investigate the role of PcG protein complex in self-renewal of the hepatic stem cells, we performed functional analyses of Ring1B that is essential for gene silencing by coupling with Bmi1 directly. When performed functional analysis of Ring1B in hepatic stem/progenitor cells derived from <i>Ring1B</i>-KO mouse with single cell-based colony assay, self-renewal capability of hepatic stem/progenitor was inhibited. Moreover, cyclin-dependent kinase inhibitor, <i>ink4a</i> and <i>arf</i> genes that were thought to be target genes of Bmi1, were depressed in <i>Ring1B</i>-KO cells.<br> These results indicate that Bmi1 and Ring1B are critical factor to self-renewal of hepatic stem/progenitor cells in the developing murine liver by suppressing a negative cell cycle regulators including <i>Ink4a</i>/<i>Arf.</i><br>

Journal

  • SEIBUTSU BUTSURI KAGAKU

    SEIBUTSU BUTSURI KAGAKU 53(4), 115-119, 2009-12-15

    Japanese Electrophoresis Society

References:  24

Codes

  • NII Article ID (NAID)
    10026143099
  • NII NACSIS-CAT ID (NCID)
    AN00129729
  • Text Lang
    JPN
  • Article Type
    REV
  • ISSN
    00319082
  • NDL Article ID
    10550006
  • NDL Source Classification
    ZR2(科学技術--生物学--生化学)
  • NDL Call No.
    Z18-127
  • Data Source
    CJP  NDL  J-STAGE 
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