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Transcriptional profiling of human embryonic stem cells differentiating to definitive and primitive endoderm and further towards the hepatic lineage
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.ORCID iD: 0000-0003-4697-0590
Cellartis AB, Göteborg.
Cellartis AB, Göteborg.
Cellartis AB, Göteborg.
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2010 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 19, no 7, 961-978 p.Article in journal (Refereed) Published
Abstract [en]

Human embryonic stem cells (hESC) can differentiate into a variety of specialized cell types, and they constitute a useful model system to study embryonic development in vitro. In order to fully utilize the potential of these cells, the mechanisms that regulate the developmental processes of specific lineage differentiation need to be better defined. The aim of this study was to explore the molecular program involved in the differentiation of hESC towards definitive endoderm (DE) and further into the hepatic lineage, and to compare that to primitive endoderm (PrE) differentiation. To that end, we applied two protocols, a specific DE differentiation protocol and an intrinsic differentiation protocol that mainly mediates PrE formation. We collected hESC, hESC-derived DE, DE-derived hepatocyte-progenitors (DE-Prog), DE-derived hepatocyte-like cells (DE-Hep), and the corresponding PrE-derivatives. The samples were analyzed using microarrays, and we identified sets of genes which were exclusively up-regulated in DE-derivatives (compared to PrE-derivatives) at discrete developmental stages. We also investigated known protein interactions among the set of up-regulated genes in DE-Hep. The results demonstrate important differences between DE- and PrE-differentiation on the transcriptional level. In particular, our results identify a unique molecular program, exclusively activated during development of DE and the subsequent differentiation of DE towards the hepatic lineage. We identified key-genes and pathways of potential importance for future efforts to improve hepatic differentiation from hESC. These results reveal new opportunities for rational design of specific interventions with the purpose of generating enriched populations of DE derivatives, including functional hepatocytes.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2010. Vol. 19, no 7, 961-978 p.
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-3660DOI: 10.1089/scd.2009.0220ISI: 000279976900003PubMedID: 19757991Scopus ID: 2-s2.0-77954896478OAI: oai:DiVA.org:his-3660DiVA: diva2:292479
Available from: 2010-02-08 Created: 2010-02-08 Last updated: 2014-11-27Bibliographically approved

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Synnergren2010(1476 kB)508 downloads
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