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Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.

ABSTRACT: 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.

SUBMITTER: Gupta MK

PROVIDER: S-EPMC2946283 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.

Gupta Manoj K MK 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

BMC developmental biology 20100915

<h4>Background</h4>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.<h4>Results</h4>Hierarchical clustering and principal component analysis revealed that iPS-BCs and ES-BCs cluster together, are simil ...[more]

PMID: 20843318

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Project description:An understanding of the regulatory mechanisms responsible for pluripotency in embryonic stem cells (ESCs) is critical for realizing their potential in medicine and science. Significant similarities exist among ESCs harvested from different species, yet major differences have also been observed. Here, by cross-species analysis of a large set of functional categories and all transcription factors and growth factors, we reveal conserved and divergent functional landscapes underlining fundamental and species-specific mechanisms that regulate ESC development. Global transcriptional trends derived from all expressed genes, instead of differentially expressed genes alone, were examined, allowing for a higher discriminating power in the functional portrait. We demonstrate that cross-species correlation of transcriptional changes that occur upon ESC differentiation is a powerful predictor of ESC-important biological pathways and functional cores within a pathway. Hundreds of functional modules, as defined by Gene Ontology, were associated with conserved expression patterns but bear no overt relationship to ESC development, suggestive of new mechanisms critical to ESC pluripotency. Yet other functional modules were not conserved; instead, they were significantly up-regulated in ESCs of either species, suggestive of species-specific regulation. The comparisons of ESCs across species and between human ESCs and embryonal carcinoma stem cells suggest that while pluripotency as an essential function in multicellular organisms is conserved throughout evolution, mechanisms primed for differentiation are less conserved and contribute substantially to the differences among stem cells derived from different tissues or species. Our findings establish a basis for defining the "stemness" properties of ESCs from the perspective of functional conservation and variation. The data and analyses resulting from this study provide a framework for new hypotheses and research directions and a public resource for functional genomics of ESCs.

Dataset Information

Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.

Publications

Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar.

Similar Datasets

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