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Research progress

2012-2013: Proposed research project 18

3D analysis on the dynamic behavior of the biliary system under normal and liver injury conditions using a novel visualization technique
Leader : Tohru Itoh
Research progress

In this research project, we have so far obtained the following findings. First, 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 so-called liver progenitor cells (LPCs) that are induced to emerge and expand upon liver injury form the contiguous tubular structure connected to the pre-existing biliary epithelial cells (BECs). Moreover, comparison of various injury models has revealed the diverse and adaptive architectures of the growing biliary tree, corresponding to the nature of injuries (unpublished data). Second, we have found by genetic lineage tracing approach in mice that LPCs/BECs can indeed produce new hepatocytes close to the site of parenchymal injury under certain types of liver disease conditions, thereby functionally contributing to the process of liver regeneration (unpublished data). Finally, based on the single cell labeling and fate tracing analyses in vivo, we have found that BECs do not proliferate uniformly but rather harbor a subpopulation that is capable of undergoing clonal expansion upon liver injury, suggesting the existence of a specific progenitor cell population in the mouse biliary system. In addition, a relationship between the location of such a proliferative population and 3D structure of the biliary tree has been noticed (unpublished data).