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Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0003-2942-6702
University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. (Bioinformatik, Bioinformatics)ORCID iD: 0000-0001-6254-4335
Takara Bio Europe AB, Gothenburg, Sweden.
Takara Bio Europe AB, Gothenburg, Sweden.
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2016 (English)In: Stem Cells International, ISSN 1687-9678, Vol. 2016, 8648356Article in journal (Refereed) Published
Abstract [en]

Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

Place, publisher, year, edition, pages
2016. Vol. 2016, 8648356
National Category
Cell Biology
URN: urn:nbn:se:his:diva-12033DOI: 10.1155/2016/8648356ISI: 000373503900001PubMedID: 26949401ScopusID: 2-s2.0-84959330405OAI: oai:DiVA.org:his-12033DiVA: diva2:911904
Available from: 2016-03-14 Created: 2016-03-14 Last updated: 2016-06-08Bibliographically approved

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