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Summary: This protocol describes the generation of bipotent chemically derived hepatic progenitors (mCdHs) from mouse primary hepatocytes and their subsequent differentiation into either hepatic or cholangiocytic lineages. The reprogrammed mCdHs have a high proliferation capacity and express progenitor markers in long-term passages. Differentiated mCdHs show the characteristics of either hepatic or cholangiocytic genes. This protocol has potential application for regenerative medicine, including ex vivo gene therapy, disease modeling, drug screening, and personalized medicine.For complete details on the use and execution of this protocol, please refer to Kim et al. (2021).