It is important to understand the property of stem cells in normal and abnormal tissues for future regenerative medicine and cancer therapy. We have developed a method of prospective isolation for hepatic stem cells and revealed molecular mechanisms underlying their differentiation and proliferation (Suzuki et al., Hepatology, 2000 & 2008; Suzuki et al., J Cell Biol, 2002; Suzuki et al., Development, 2003 & 2008; Onoyama et al., J Clin Invest, 2011). We also found that hepatic stem cells could turn into malignant cancer stem-like cells in the result of gene deletion and unveiled a mechanism that regulates stem cell-independent liver regeneration (Suzuki et al., Hepatology, 2008; Sekiya and Suzuki, PNAS, 2011). Moreover, we succeeded in induction of the lineage-conversion of mouse fibroblasts to hepatocyte-like cells (iHep cells) by introducing three specific combinations of two transcription factors (Sekiya and Suzuki, Nature, 2011; Miura and Suzuki, Front Cell Dev Biol, 2014; Miura and Suzuki, Inflamm Renen, 2014). Our recent studies also demonstrated that intrahepatic cholangiocarcinoma and the ductular reaction (an increase of primitive ductules in the chronically injured liver), both of which have been thought as derivatives of intrahepatic cholangiocytes, arise from hepatocytes by Notch-mediated cell lineage conversion (Sekiya and Suzuki, J Clin Invest, 2012; Sekiya and Suzuki, Am J Pathol, 2014). And, more recently, we succeeded in constructing a three-dimensional dynamic model of intrahepatic bile duct formation, through quantitative analyses with spatiotemporal observations using a three-dimensional structural reconstruction model and morphometrics (Takashima et al., Hepatology, 2015).