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Stem Cell Genetics and Genomics |
1 Hubrecht Laboratory, Uppsalalaan, Utrecht, Netherlands
2 Hubrecht Laboratory, Uppsalalaan, Utrecht, Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, Netherlands
* To whom correspondence should be addressed. E-mail: christin{at}niob.knaw.nl.
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Abstract |
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Mammals are unable to regenerate their heart after major cardiomyocyte loss caused by myocardial infarction. Human embryonic stem cells (hESCs) can give rise to functional cardiomyocytes and therefore have exciting potential as a source of cells for replacement therapy. Understanding the molecular regulation of cardiomyocyte differentiation from stem cells is crucial for the step-wise enhancement and scaling of cardiomyocyte production that will be necessary for transplantation therapy. Our novel hESC differentiation protocol is now efficient enough for meaningful genome-wide transcriptional profiling by microarray technology of hESCs, differentiating towards cardiomyocytes. Here, we have identified and validated time-dependent gene expression patterns and shown a reflection of early embryonic events; induction of genes of the primary mesoderm and endodermal lineages is followed by those of cardiac progenitor cells and fetal cardiomyocytes in consecutive waves of known and novel genes. Collectively, these results permit enhancement of step-wise differentiation and facilitate isolation and expansion of cardiac progenitor cells. Furthermore, these genes may provide new clinically relevant clues for identifying causes of congenital heart defects.
Key Words. human embryonic stem cells (hESCs), cardiomyocytes, microarrays, transcriptional profiling, gene expression, differentiation
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