Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.
BACKGROUND
Functional and molecular integrity of cardiomyocytes (CMs) derived from induced pluripotent stem (iPS) cells is essential for their use in tissue repair, disease modelling and drug screening. In this study we compared global transcriptomes of beating clusters (BCs) microdissected from differentiating human iPS cells and embryonic stem (ES) cells.


RESULTS
Hierarchical clustering and principal component analysis revealed that iPS-BCs and ES-BCs cluster together, are similarly enriched for cardiospecific genes and differ in expression of only 1.9% of present transcripts. Similarly, sarcomeric organization, electrophysiological properties and calcium handling of iPS-CMs were indistinguishable from those of ES-CMs. Gene ontology analysis revealed that among 204 genes that were upregulated in iPS-BCs vs ES-BCs the processes related to extracellular matrix, cell adhesion and tissue development were overrepresented. Interestingly, 47 of 106 genes that were upregulated in undifferentiated iPS vs ES cells remained enriched in iPS-BCs vs ES-BCs. Most of these genes were found to be highly expressed in fibroblasts used for reprogramming and 34% overlapped with the recently reported iPS cell-enriched genes.


CONCLUSIONS
These data suggest that iPS-BCs are transcriptionally highly similar to ES-BCs. However, iPS-BCs appear to share some somatic cell signature with undifferentiated iPS cells. Thus, iPS-BCs may not be perfectly identical to ES-BCs. These minor differences in the expression profiles may occur due to differential cellular composition of iPS-BCs and ES-BCs, due to retention of some genetic profile of somatic cells in differentiated iPS cell-derivatives, or both.
Gupta
Manoj K
MK
Center for Physiology and Pathophysiology, Institute for Neurophysiology, University of Cologne, Robert-Koch-Str 39, 50931 Cologne, Germany.
Illich
Damir J
DJ
Gaarz
Andrea
A
Matzkies
Matthias
M
Nguemo
Filomain
F
Pfannkuche
Kurt
K
Liang
Huamin
H
Classen
Sabine
S
Reppel
Michael
M
Schultze
Joachim L
JL
Hescheler
Jürgen
J
Sarić
Tomo
T
D020013:Calcium Signaling; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D052816:Foreskin / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D014158:Transcription, Genetic