Three-dimensional imaging and morphometric analysis on proliferation of pseudo-biliary tracts and differentiation into cholangiocarcinomas

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19025
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: TAKASHIMA Yasuo 九州大学, 生体防御医学研究所, 特任助教 (50621083)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 肝内胆管癌 / 分化転換 / Notchシグナル / Kupffer細胞 / アポトーシス / 肝前駆細胞 / LIN28B / miRNA

Outline of Final Research Achievements

For chronic diseases and cancers in liver, it is desirable to diagnose the three-dimensional (3D) structures of lesions and altered microtubule structures on a single cell-based observation. In this study, we purpose to develop technical infrastructures for pathological diagnosis and basic medicine, based on morphometrics for proliferation of pseudo-biliary tracts and cholangiocarcinomas, derived from pseudo-biliary epithelial cells differentiated from hepatocytes, using a high-resolution digital 3D reconstruction. Here we showed that Kupffer cells, known as stellate macrophages, stimulate Notch signaling in hepatocytes surrounding central veins, therefore, hepatocytes can be reprogrammed into bile duct-like cells without apoptosis. We also demonstrated that LIN28B, in hepatoblasts, suppresses tumor suppressive miRNAs including miR-125a/b and let-7b, and maintains expression of LIN28B itself, thereby, regulating their proliferation and suppressing differentiation into biliary cells.

Free Research Field

細胞生物学・生理形態学