Submitted on July 10, 2008
Revised on February 25, 2009
Accepted on March 12, 2009
Genomic profiling of developing cardiomyocytes from recombinant murine embryonic stem cells reveals regulation of transcription factor clusters
Michael J. Seewald1, Peter Ellinghaus1, Astrid Kassner2, Ines Stork2, Martina Barg1, Sylvia Niebrügge3, Stefan Golz1, Holger Summer1, Robert Zweigerdt4, Eva-Maria Schräder2, Samantha Feicht2, Kornelia Jaquet5, Stephanie Reis5, Reiner Körfer2, and Hendrik Milting2*
1 Bayer Healthcare AG
2 Herz- & Diabeteszentrum NRW
3 University of Toronto
4 Institute of Medical Biology
5 Berufsgenossenschaftliche Kliniken Bergmannsheil
* To whom correspondence should be addressed. E-mail: hmilting{at}hdz-nrw.de.
Cardiomyocytes derived from pluripotent embryonic stem cells (ESC) have the advantage of providing a source for standardized cell cultures. However, little is known on the regulation of the genome during differentiation of ESC to cardiomyocytes. Here, we characterize the transcriptome of the mouse embryonic stem cell line CM7/1 during differentiation into beating cardiomyocytes and compare the gene expression profiles with those from primary adult murine cardiomyocytes and left ventricular myocardium. We observe that the cardiac gene expression pattern of fully differentiated CM7/1-ESC is highly similar to adult primary cardiomyocytes and murine myocardium, respectively. This finding is underlined by demonstrating pharmacological effects of catecholamines and endothelin 1 on ESC-derived cardiomyocytes. Furthermore, we monitor the temporal changes in gene expression pattern during ESC differentiation with a special focus on transcription factors involved in cardiomyocyte differentiation. Thus, CM7/1-ESC-derived cardiomyocytes are a promising new tool for functional studies of cardiomyocytes in vitro and for the analysis of the transcription factor network regulating pluripotency and differentiation to cardiomyocytes.
