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Global transcriptional profiling reveals similarities and differences between human stem cell-derived cardiomyocyte clusters and heart tissue
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. Department of Clinical Chemistry/Transfusion Medicine, Sahlgrenska University Hospital. (Infektionsbiologi, Infection Biology)ORCID iD: 0000-0003-4697-0590
Cellartis, Göteborg, Sweden.
University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre. (Infektionsbiologi, Infection Biology)
Cellartis, Göteborg, Sweden.
2012 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, no 4, 245-258 p.Article in journal (Refereed) Published
Abstract [en]

It is now well documented that human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes. These cells constitute a promising source of material for use in drug development, toxicity testing, and regenerative medicine. To assess their utility as replacement or complement to existing models, extensive phenotypic characterization of the cells is required. In the present study, we used microarrays and analyzed the global transcription of hESC-derived cardiomyocyte clusters (CMCs) and determined similarities as well as differences compared with reference samples from fetal and adult heart tissue. In addition, we performed a focused analysis of the expression of cardiac ion channels and genes involved in the Ca2+-handling machinery, which in previous studies have been shown to be immature in stem cell-derived cardiomyocytes. Our results show that hESC-derived CMCs, on a global level, have a highly similar gene expression profile compared with human heart tissue, and their transcriptional phenotype was more similar to fetal than to adult heart. Despite the high similarity to heart tissue, a number of significantly differentially expressed genes were identified, providing some clues toward understanding the molecular difference between in vivo sourced tissue and stem cell derivatives generated in vitro. Interestingly, some of the cardiacrelated ion channels and Ca2+-handling genes showed differential expression between the CMCs and heart tissues. These genes may represent candidates for future genetic engineering to create hESC-derived CMCs that better mimic the phenotype of the cardiomyocytes present in the adult human heart.

Place, publisher, year, edition, pages
American Physiological Society , 2012. Vol. 44, no 4, 245-258 p.
Keyword [en]
cardiomyocytes, human embryonic stem cells, differentiation, gene xpression, Ca2+ handling, ion channels
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-5668DOI: 10.1152/physiolgenomics.00118.2011ISI: 000300883700002PubMedID: 22166955Scopus ID: 2-s2.0-84857762746OAI: oai:DiVA.org:his-5668DiVA: diva2:513346
Available from: 2012-04-02 Created: 2012-04-02 Last updated: 2014-11-27Bibliographically approved

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