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Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2012 Jan; Vol. 20 (1), pp. 127-37. Date of Electronic Publication: 2011 Nov 08. - Publication Year :
- 2012
-
Abstract
- Hepatocyte-like cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are expected to be a useful source of cells drug discovery. Although we recently reported that hepatic commitment is promoted by transduction of SOX17 and HEX into human ESC- and iPSC-derived cells, these hepatocyte-like cells were not sufficiently mature for drug screening. To promote hepatic maturation, we utilized transduction of the hepatocyte nuclear factor 4α (HNF4α) gene, which is known as a master regulator of liver-specific gene expression. Adenovirus vector-mediated overexpression of HNF4α in hepatoblasts induced by SOX17 and HEX transduction led to upregulation of epithelial and mature hepatic markers such as cytochrome P450 (CYP) enzymes, and promoted hepatic maturation by activating the mesenchymal-to-epithelial transition (MET). Thus HNF4α might play an important role in the hepatic differentiation from human ESC-derived hepatoblasts by activating the MET. Furthermore, the hepatocyte like-cells could catalyze the toxication of several compounds. Our method would be a valuable tool for the efficient generation of functional hepatocytes derived from human ESCs and iPSCs, and the hepatocyte-like cells could be used for predicting drug toxicity.
- Subjects :
- Cell Differentiation
Cell Line
Embryonic Stem Cells metabolism
Epithelial-Mesenchymal Transition genetics
Gene Transfer Techniques
Hepatocyte Nuclear Factor 4 metabolism
Hepatocytes metabolism
Humans
Induced Pluripotent Stem Cells metabolism
Proto-Oncogene Proteins c-met metabolism
Time Factors
Embryonic Stem Cells cytology
Hepatocyte Nuclear Factor 4 genetics
Hepatocytes cytology
Induced Pluripotent Stem Cells cytology
Transduction, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 22068426
- Full Text :
- https://doi.org/10.1038/mt.2011.234