Expression of ErbB receptors in ES cell-derived cardiomyocytes.
To explore the role of ErbB-mediated signaling in cardiogenesis of ES cells, we examined the expression of ErbB receptors as well as effects of a ligand and inhibitors using Nkx2.5GFP ES cells, in which the GFP gene was knocked-in to the Nkx2.5 locus to monitor cardiac differentiation. Although all ErbB receptors were expressed in developing embryoid bodies, expression of ErbB4 was almost exclusively found in differentiated cardiomyocytes. Heregulin beta1, a ligand of ErbB receptors, enhanced the generation of Nkx2.5/GFP(+) cardiomyocytes in embryoid bodies, while AG1478 and PD153035, inhibitors of ErbBs, drastically blocked the generation of Nkx2.5/GFP(+) cardiomyocytes. These results suggest that the signaling pathway mediated by ErbBs is important in the induction and differentiation of cardiomyocytes from ES cells.
Suk Kim
Hoe
H
Department of Bioscience, National Cardiovascular Center Research Institute, 5-7-1, Fujishirodai, Suita, Osaka, Japan.
Hidaka
Kyoko
K
Morisaki
Takayuki
T
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis*; D049452:Green Fluorescent Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology*; D020890:Neuregulin-1 / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors; D020032:Tyrphostins / Q000494:pharmacology; D029867:Xenopus Proteins / Q000378:metabolism
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D008024:Ligands; D008164:Luminescent Proteins; C095552:NKX2-5 protein, human; D020890:Neuregulin-1; C484469:Nkx2-5 protein, mouse; D011799:Quinazolines; D014157:Transcription Factors; D020032:Tyrphostins; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; C087230:heregulin beta1; C101044:RTKI cpd; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline