Abstract
Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) differentiated into hepatocyte-like cells (HLCs) provide a defined and renewable source of cells for drug screening, toxicology and regenerative medicine. We previously reprogrammed human fetal foreskin fibroblast cells (HFF1) into iPSCs employing an episomal plasmid-based integration-free approach, this iPSC-line and the hESC lines H1 and H9 were used to model hepatogenesis in vitro. Biochemical characterisation confirmed glycogen storage, ICG uptake and release, urea and bile acid production, as well as CYP3A4 activity. Microarray-based transcriptome analyses was carried out using RNA isolated from the undifferentiated pluripotent stem cells and subsequent differentiation stages- definitive endoderm (DE) hepatic endoderm (HE) and HLCs. K-means identified 100 distinct clusters, for example, POU5F1/OCT4 marking the undifferentiated stage, SOX17 the DE stage, HNF4α the HE stage, and ALB specific to HLCs, fetal liver and primary human hepatocytes (PHH). This data descriptor describes these datasets which should be useful for gaining new insights into the molecular basis of hepatogenesis and associated gene regulatory networks.
Highlights
Background & SummaryThe implementation of a well-characterized renewable source of hepatocytes differentiated from Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) provides a powerful in vitro model system for analysing the molecular mechanisms associated with hepatogenesis
The implementation of a well-characterized renewable source of hepatocytes differentiated from iPSCs and hESCs provides a powerful in vitro model system for analysing the molecular mechanisms associated with hepatogenesis
Available liver cellular models have disadvantages: (i) liver biopsy derived primary human hepatocytes (PHH) cannot be expanded for long periods in vitro, are often obtained from diseased individuals and are difficult to obtain in sufficient quantities[5,6], (ii) transformed, permanent cell lines, such as HepG2 and HepaRG, have cancer phenotypes which are significantly diverged from normal primary hepatocytes[7,8,9]
Summary
The implementation of a well-characterized renewable source of hepatocytes differentiated from iPSCs and hESCs provides a powerful in vitro model system for analysing the molecular mechanisms associated with hepatogenesis. Several essential initiators of hepatogenesis such as fibroblast growth factor 2 and 4 (FGF4 and FGF2)[1,2], bone morphogenic protein (BMP2)[3], hepatocyte growth factor (HGF), oncostatin M and dexamethasone[4] have already been described. These factors are sequentially supplemented into the media during the course of the differentiation process. The data described consists of microarray gene expression data from hESCs and hiPSCs differentiated into HLCs via the DE and HE stages and fetal liver and primary human hepatocyte samples as reference. Transcription factors central to hepatogenesis have been described, the datasets described here will enable a more detailed analyses of gene regulatory networks associated with modelling hepatogenesis using pluripotent stem cells
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