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Figure 3. The hierarchy of cholangiocarcinoma stem cells. Hepatic progenitor/stem cells differentiate into hepatocytes and cholangiocytes. Through carcinogenesis involving various factors, these cells can develop into HCC and CCA, respectively. Moreover, hepatic progenitor/stem cells with genetic abnormalities can reprogram into CCA-CSCs or HCC cells. These abnormal cells then proliferate and differentiate to form CCA and HCC cells. Additionally, hepatocytes can act as stem-like cells in the liver and possess the ability to reprogram into CCA-CSCs, suggesting that mature hepatocytes may serve as an origin of CCA through genetic and epigenetic alterations, as well as influences from the microenvironment. CSC: Cancer stem cell; CCA: cholangiocarcinoma; HCC: hepatocellular carcinoma.