In this research project, we have so far obtained the following achievements:

(1) We have succeeded in visualizing the fine 3D structure of the whole biliary tree within mouse liver samples. This has enabled us to demonstrate that liver progenitor cells (LPCs) that are induced to emerge and expand upon liver injury actually form the contiguous tubular structure connected to the pre-existing biliary tree. Moreover, comparison of various injury models has revealed the diverse architectures of the growing biliary tree, which are well adapted to the nature of injuries (Kaneko et al., Hepatology, 2015). (2) Based on the single-cell labeling and fate tracing analyses in vivo, we have shown that those cells comprising the biliary tree do not proliferate uniformly; rather, a clonally expanding subpopulation emerges and is maintained stochastically during the course of liver injury, thereby making a major contribution in sustaining the biliary expansion (unpublished data). (3) We have found that a member of the KLF family transcription factor plays an important role in regulating proliferation of the biliary epithelial tissue upon certain types of liver injury (unpublished data).

(4) We have established an intravital multi-dimensional imaging platform to observe and trace the dynamics of fluorescently labeled hepatocytes and biliary epithelial cells, as well as the blood and bile flows, in the liver using living mice. Based on this approach, we have found that the bile flow undergoes dynamic changes upon liver injury, which affects the biliary epithelial tissue remodeling (unpublished data).