title: Molecular signature of cardiomyocyte clusters derived from human embryonic stem cells.
abstract: 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.
authors.affiliation: School of Humanities and Informatics, University of Skövde, P.O. Box 408, SE-541 28 Skövde, Sweden. jane.synnergren@his.se
authors.forename: Jane
authors.initials: J
authors.lastname: Synnergren
authors.forename: Karolina
authors.initials: K
authors.lastname: Akesson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dahlenborg
authors.forename: Hilmar
authors.initials: H
authors.lastname: Vidarsson
authors.forename: Caroline
authors.initials: C
authors.lastname: Améen
authors.forename: Daniella
authors.initials: D
authors.lastname: Steel
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
authors.forename: Björn
authors.initials: B
authors.lastname: Olsson
authors.forename: Peter
authors.initials: P
authors.lastname: Sartipy
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D046149:Embryo Culture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D025941:Protein Interaction Mapping; D015854:Up-Regulation