Document Detail


Transforming pluripotency: an exon-level study of malignancy-specific transcripts in human embryonal carcinoma and embryonic stem cells.
MedLine Citation:
PMID:  23137282     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To circumvent difficulties of isolating pure populations of cancer stem cells (CSCs) for the purpose of identifying malignancy-specific gene expression, we have compared exon-resolution transcriptomic profiles of 5 embryonal carcinoma (EC) cell lines, a histological subtype of germ cell tumor (GCT), to their nonmalignant caricature, specifically 6 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. Expression of these 28 genes was further explored within 2 publically available data sets of primary EC tumors and normal testis. 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 reverse transcriptase-polymerase chain reaction-based methods in EC and ES lines, 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 GCT and ES cell biology, and, in general, to the concept of CSCs.
Authors:
Sharmini Alagaratnam; Neil Harrison; Anne Cathrine Bakken; Andreas M Hoff; Mark Jones; Anita Sveen; Harry D Moore; Peter W Andrews; Ragnhild A Lothe; Rolf I Skotheim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-04
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-02     Completed Date:  2013-09-25     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1136-46     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing
Carcinoma, Embryonal / metabolism*
Cell Differentiation
Cell Line
Cell Line, Tumor
Cell Transformation, Neoplastic
DNA (Cytosine-5-)-Methyltransferase / genetics
DNA-Binding Proteins / genetics
Embryonal Carcinoma Stem Cells / metabolism*
Embryonic Stem Cells / metabolism*
Gene Expression Profiling
Gene Expression Regulation, Developmental*
Humans
Nuclear Proteins / genetics
Pluripotent Stem Cells / metabolism*
Receptors, Cytoplasmic and Nuclear / biosynthesis,  genetics
Transcription Factors / genetics
Transcriptome
Wnt Signaling Pathway / genetics
Grant Support
ID/Acronym/Agency:
G0700785//Medical Research Council; G0801059//Medical Research Council
Chemical
Reg. No./Substance:
0/ASH2L protein, human; 0/DNA-Binding Proteins; 0/ETV5 protein, human; 0/NR5A2 protein, human; 0/Nuclear Proteins; 0/PMF1 protein, human; 0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factors; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA methyltransferase 3B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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