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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-1033v1 26/7/1831    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Google Scholar Articles by Synnergren, J. Articles by Sartipy, P. PubMed PubMed Citation Articles by Synnergren, J. Articles by Sartipy, P.

EMBRYONIC STEM CELLS

Molecular Signature of Cardiomyocyte Clusters Derived from Human Embryonic Stem Cells

^aSchool of Life Science, University of Skövde, Skövde, Sweden;
^bDepartment of Clinical Chemistry/Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden;
^cCellartis AB, Göteborg, Sweden

Key Words. Human embryonic stem cells • Differentiation • Cardiomyocytes • Gene expression

Correspondence: Jane Synnergren, MSc., School of Humanities and Informatics, University of Skövde, P.O. Box 408, SE-541 28 Skövde, Sweden. Telephone: +46(0)500-448-311; Fax: +46(0)500-448-399; e-mail: jane.synnergren{at}his.se; or Peter Sartipy, Ph.D., Cellartis AB, Arvid Wallgrens Backe 20, SE-413 46 Göteborg, Sweden. Telephone: +46(0)31-758-0930; Fax: +46(0)31-758-0910; e-mail: peter.sartipy{at}cellartis.com

Received December 7, 2007; accepted for publication April 4, 2008.
First published online in STEM CELLS EXPRESS   April 24, 2008.

Human embryonic stem cells (hESCs) can differentiate in vitro into spontaneously contracting cardiomyocytes (CMs). These cells may prove extremely useful for various applications in basic research, drug discovery, and regenerative medicine. To fully use the potential of the cells, they need to be extensively characterized, and the regulatory mechanisms that control hESC differentiation toward the cardiac lineage need to be better defined. In this study, we used microarrays to analyze, for the first time, the global gene expression profile of isolated hESC-derived CM clusters. By comparing the clusters with undifferentiated hESCs and using stringent selection criteria, we identified 530 upregulated and 40 downregulated genes in the contracting clusters. To further characterize the family of upregulated genes in the hESC-derived CM clusters, the genes were classified according to their Gene Ontology annotation. The results indicate that the hESC-derived CM clusters display high similarities, on a molecular level, to human heart tissue. Moreover, using the family of upregulated genes, we created protein interaction maps that revealed topological characteristics. We also searched for cellular pathways among the upregulated genes in the hESC-derived CM clusters and identified eight significantly upregulated pathways. Real-time quantitative polymerase chain reaction and immunohistochemical analysis confirmed the expression of a subset of the genes identified by the microarrays. Taken together, the results presented here provide a molecular signature of hESC-derived CM clusters and further our understanding of the biological processes that are active in these cells.

Disclosure of potential conflicts of interest is found at the end of this article.