Genomic profiling of developing cardiomyocytes from recombinant murine embryonic stem cells reveals regulation of transcription factor clusters.
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 ESC 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.
Seewald
Michael J
MJ
Department of Target Discovery, Bayer Healthcare AG, Wuppertal, Germany.
Ellinghaus
Peter
P
Kassner
Astrid
A
Stork
Ines
I
Barg
Martina
M
Niebrügge
Sylvia
S
Golz
Stefan
S
Summer
Holger
H
Zweigerdt
Robert
R
Schräder
Eva-Maria
EM
Feicht
Samantha
S
Jaquet
Kornelia
K
Reis
Stephanie
S
Körfer
Reiner
R
Milting
Hendrik
H
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D014157:Transcription Factors