 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 01, 2015 |
| Title |
Transforming pluripotency: an exon-level study of malignancy-specific transcripts in human embryonal carcinoma and embryonic stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Exon-level transcriptome analysis of embryonal carcinoma (EC) and embryonic stem (ES) cell lines.
To circumvent difficulties of isolating pure populations of cancer stem cells for the purpose of identifying malignancy-specific gene expression, we have compared exon-resolution transcriptomic profiles of five embryonal carcinoma (EC) cell lines, a histological subtype of germ cell tumour, to their non-malignant caricature, specifically six human embryonic stem (ES) cell lines. Both cell types are readily accessible, and were purified for undifferentiated cells only. We identified a set of 28 differentially expressed genes, many of which had cancer and stemness roles. Overexpression of the recently discovered pluripotency gene NR5A2 in malignant EC cells revealed an intriguing indication of how WNT-mediated dysregulation of pluripotency is involved with malignancy. At the exon-level, alternative splicing events were detected in ZNF195, DNMT3B and PMF1, and alternative promoters were detected for ASH2L and ETV5. These events were validated by RT-PCR-based methods in EC and ES lines, and further explored within a series of 25 primary tumours, where the alternative splicing event in the de novo DNA methyltransferase DNMT3B may have functional consequences. In conclusion, we have identified malignancy-specific gene expression differences within a rigorous pluripotent stem cell context. These findings are of particular interest for both germ cell tumour and ES cell biology, and in general to the concept of cancer stem cells.
|
| |
|
| Overall design |
5 EC and 6 ES cell lines gown on plastic and feeders respectively were sorted for the pluripotency marker SSEA3, then profiled on the Affymetrix Human Exon 1.0 ST platform. 3 additional EC lines grown on feeders and ES medium were also profiled in the same way. Data was analyzed using Qlucore (PCA), XRAY and limma (gene- and exon-level expression differences) and SAM (two-class pair-wise Significance of Microarrays).
|
| |
|
| Contributor(s) |
Alagaratnam S, Harrison N, Bakken AC, Hoff A, Jones M, Sveen A, Moore HD, Andrews PW, Lothe RA, Skotheim RI |
| Citation(s) |
23137282 |
| Submission date |
Jan 04, 2012 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Sharmini Alagaratnam |
| E-mail(s) |
sharm@rr-research.no
|
| Organization name |
Oslo University Hospital
|
| Department |
Institute for Cancer Research
|
| Lab |
Dept of Molecular Oncology
|
| Street address |
Radiumhospitalet, Montebello
|
| City |
Oslo |
| ZIP/Postal code |
0310 |
| Country |
Norway |
| |
|
| Platforms (2) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
| GPL5188 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [probe set (exon) version] |
|
| Samples (28)
|
|
| Relations |
| BioProject |
PRJNA150117 |
|
|
|
|
 |
Less...
More...