Abstract
BackgroundFunctional 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.ResultsHierarchical 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.ConclusionsThese 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.
Highlights
Functional and molecular integrity of cardiomyocytes (CMs) derived from induced pluripotent stem cells is essential for their use in tissue repair, disease modelling and drug screening
Cardiac differentiation of human induced pluripotent stem (iPS) and embryonic stem (ES) cells The human iPS cell line derived from foreskin fibroblasts, clone 1 (C1), [6] and the human ES cell line HES-2 were differentiated to CMs using the END2 coculture system [15] (Additional file 1, Figure S1)
By comparing these data with our list of 47 transcripts upregulated in iPS cells and iPS-beating clusters (BC) we found that 16 of these transcripts (34%) were detected in these previous studies to be expressed in multiple human iPS cell lines in comparison with various ES cell lines (Table 1)
Summary
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. Initial studies have demonstrated that diverse types of mature cell derivatives of all three embryonic germ layers can be differentiated from iPS cells [7,8,9,10,11,12]. The comparison of global transcriptomes of mature cells differentiated from ES and iPS cells has not yet been performed, and it is not clear whether molecular differences between iPS and ES cells are retained upon their differentiation into mature cells
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