Molecular mechanism underlying maintenance and differentiation of tissue-specific stem cells

2015 Fiscal Year Final Research Report

• Project Area: Regulation of polarity signaling during morphogenesis, remodeling, and breakdown of epithelial tubular structure
• Project/Area Number: 23112002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University
• Principal Investigator: Suzuki Atsushi 九州大学, 生体防御医学研究所, 教授 (30415195)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 上皮管腔組織 / 幹細胞 / 肝臓 / 発生 / 再生 / 癌 / 細胞分化

Outline of Final Research Achievements

In this study, we focused on tissue stem cells that provide various epithelial cells forming tubule structures. In our previous studies, we have developed a method to prospectively isolate hepatic stem cells residing in the developing mouse liver, called hepatoblasts, and thus, we sought to elucidate molecular mechanisms underlying maintenance and differentiation of hepatoblasts. Our analyses revealed essential roles of transcription factors and microRNAs in regulation of the differentiation and proliferation of hepatoblasts. Moreover, we unveiled a mechanism that regulates initiation of hepatocyte proliferation in liver regeneration, succeeded in inducing conversion of mouse fibroblasts to hepatocyte-like cells, found that intrahepatic cholangiocarcinoma and the ductular reaction caused in the chronically injured liver arise from hepatocytes by Notch-mediated cell-fate conversion, and succeeded in constructing a three-dimensional dynamic model of intrahepatic bile duct formation.

Free Research Field

発生生物学、幹細胞生物学、再生医学