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Updated: Feb 18, 2026
Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System
Published on: May 10, 2020
Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells Produced by Different Strategies from the
Yimeng Gao1, Xiaoran Zhang2, Ludi Zhang1
1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Abstract:
Hepatocyte-like cells (HLCs) can be generated through directed differentiation or transdifferentiation. Employing two strategies, we generated induced pluripotent stem cell (iPSC)-HLCs and hiHeps from the same donor cell line. Both types of HLCs clustered distinctly from each other during gene expression profiling. In particular, differences existed in gene expression for phase II drug metabolism and lipid accumulation, underpinned by H3K27 acetylation status in iPSC-HLCs and hiHeps. While distinct phenotypes were achieved in vitro, both types of HLCs demonstrated similar phenotypes following transplantation into Fah-deficient mice. In conclusion, functional HLCs can be obtained from the same donor using two strategies. Global gene expression defined the differences between those populations in vitro. Importantly, both HLCs displayed partial but markedly improved hepatic function following transplantation in vivo, demonstrating plasticity and the potential for cell-based modeling in the dish and cell-based therapy in the future.
