Global transcriptome analysis of murine embryonic stem cell-derived cardiomyocytes


  • M.X. Doss
  • J. Winkler
  • S. Chen
  • R. Hippler-Altenburg
  • I. Sotiriadou
  • M. Halbach
  • K. Pfannkuche
  • H. Liang
  • H. Schulz
  • O. Hummel
  • N. Huebner
  • R. Rottscheidt
  • J. Hescheler
  • A. Sachinidis


  • Genome Biology


  • Genome Biol 8 (4): R56


  • BACKGROUND: Characterisation of gene expression signatures for cardiomyocytes derived from embryonic stem (ES) cells will help define their early biological processes. RESULTS: A transgenic a-myosin heavy chain (a-MHC) ES cell lineage was generated, expressing puromycin resistance and enhanced green fluorescent protein (EGFP) under the control of the a-MHC promoter. A puromycin-resistant, EGFP+, a-MHC+ cardiomyocyte population was isolated with over 92% purity. RNA was isolated after electrophysiological characterisation of the cardiomyocytes. Comprehensive transcriptome analysis of a-MHC+ cardiomyocytes in comparison to undifferentiated a-MHC ES cells and the control population from 15-day old embryoid bodies (EBs) led to the identification of 884 upregulated probe sets and 951 downregulated probe sets in a-MHC+ cardiomyocytes. A subset of upregulated genes encodes for cytoskeletal and voltage-dependent channel proteins, and proteins participating in aerobic energy metabolism. Interestingly, mitosis, apoptosis and Wnt signalling-associated genes were downregulated in the cardiomyocytes. In contrast, annotations for genes upregulated in the a-MHC+ cardiomyocytes are enriched for the gene ontology categories: enzyme-linked receptor protein signalling pathway (GO:0007167); protein kinase activity (GO:0004672); negative regulation of Wnt receptor signalling pathway (GO:0030178); regulation of cell size (O:0008361); as well as for the Biocarta p38 MAPK signalling pathway and KEGG calcium signalling pathway. CONCLUSION: The specific pattern of gene expression in the cardiomyocytes derived from ES cells reflects the biological, physiological and functional processes occurring in mature cardiomyocytes. Identification of cardiomyocyte-specific gene expression patterns and signalling pathways will contribute towards elucidating their roles during intact cardiac function.