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Updated: Sep 1, 2025
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Defined and Scalable Generation of Hepatocyte-like Cells from Human Pluripotent Stem Cells
Published on: March 2, 2017
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Generation of functional hepatocytes by forward programming with nuclear receptors
Rute A Tomaz1,2, Ekaterini D Zacharis1,2, Fabian Bachinger1,2
1Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Elife
|August 12, 2022
Summary
Forward programming rapidly generates functional hepatocyte-like cells (HLCs) from human pluripotent stem cells (hPSCs). This simplified method bypasses lengthy differentiation protocols and enhances HLC functionality for biomedical applications.
Area of Science:
- Stem cell biology
- Hepatology
- Molecular biology
Background:
- Generating sufficient quantities of functional hepatocytes for clinical use is challenging.
- Current directed differentiation of human pluripotent stem cells (hPSCs) into hepatocyte-like cells (HLCs) is time-consuming and complex.
- Existing HLCs often lack the full functionality of primary hepatocytes.
Purpose of the Study:
- To investigate forward programming as a method to rapidly generate functional hepatocytes from hPSCs.
- To bypass limitations of traditional directed differentiation protocols.
- To explore the role of nuclear receptors in enhancing hepatocyte functionality.
Main Methods:
- Utilized the OPTi-OX platform for overexpression of key transcription factors.
- Overexpressed hepatocyte nuclear factors (HNF1A, HNF6, FOXA3) in combination with liver-expressed nuclear receptors.
- Generated forward programmed hepatocytes (FoP-Heps) from hPSCs.
Main Results:
- Forward programming enabled rapid production of FoP-Heps with functional characteristics.
- A simplified process was achieved compared to traditional differentiation.
- Overexpression of nuclear receptors like RORc enhanced specific FoP-Hep functionalities, particularly in lipid and glucose metabolism.
Conclusions:
- Forward programming offers a versatile and efficient alternative to direct differentiation for in vitro hepatocyte generation.
- This approach accelerates the production of functional hepatocytes for various biomedical applications.
- Nuclear receptors play a crucial role in optimizing hepatocyte functions generated through forward programming.
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