Medical Sciences Group/Intra-University Cooperative LaboratoriesTanaka Laboratory
(Laboratory of Stem Cell Regulation, IQB)
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Associate Professor TANAKA Minoru
Liver is a central organ for homeostasis by performing numerous functions such as metabolism, drug detoxification and production of plasma proteins. Liver is composed of hepatocytes and non-parenchymal cells that include endothelial cells, hepatic stellate cells (HSCs), biliary epithelial cells (BECs),blood cells and so on.During liver development, hepatoblasts proliferate and differentiate into both hepatocytes and BECs. Thus hepatoblasts are considered as liver stem/progenitor cells (LPCs) in the fetus. We have previously identified many cell surface markers for fetal liver cells and uncovered the cell-cell interactions regulating proliferation and differentiation of LPCs using flowcytometric analysis, cell culture system and mutant mice. Meanwhile in adult liver, “oval cells”have been considered as LPCs contributing to regeneration when liver is severely damaged. Although the nature of oval cells remained unclear for a long time, we have identified two cell surface markers for oval cells, EpCAM and TROP2, and shed light on it by the use of a cell sorter and cell culture system. However, the precise mechanisms regulating LPCs in adult liver are poorly understood. We are trying to understand the mechanisms regulating LPCs in liver diseases from the perspective of cell-cell interactions. Among the newly identified LPC markers, we recently found some genes involved in inflammation, fibrosis and liver cancer. Currently, we are also investigating the relationship of LPCs with liver fibrosis and carcinogenesis.