The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells

Area of Science:

• Stem cell biology
• Hepatology
• Developmental biology

Background:

• Deriving human hepatocytes from pluripotent stem cells is crucial for cell therapy and drug discovery.
• Current in vitro differentiation methods do not accurately mimic natural liver development.

Purpose of the Study:

• To develop an efficient protocol for generating hepatic progenitor cells and hepatocytes from chemically induced pluripotent stem cells (hCiPSCs).
• To mimic the two-stage developmental process of hepatoblasts for improved differentiation efficiency.

Main Methods:

• Chemically induced pluripotent stem cells (hCiPSCs) were used for differentiation.
• A two-stage protocol mimicking hepatoblast development was implemented.
• Single-cell RNA sequencing (scRNA-seq) was employed to analyze cell populations.

Main Results:

• The protocol efficiently generated hepatic progenitor cells from hCiPSCs.
• scRNA-seq confirmed the similarity of in vitro-derived hepatoblasts to their in vivo counterparts.
• hCiPSC-derived hepatic progenitor cells differentiated into hepatocytes with gene expression and functions comparable to primary human hepatocytes.

Conclusions:

• This study demonstrates a feasible and efficient method for generating hepatic progenitor cells and hepatocytes from hCiPSCs.
• The developed protocol successfully recapitulates key aspects of in vivo liver development.
• These findings provide a foundation for the translational application of hCiPSC-derived hepatocytes in regenerative medicine and drug development.