| Differential expression of epigenetic modulators during human embryonic stem cell differentiation. | |
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MedLine Citation:
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PMID: 18953677 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although the progression of aging and the diseases associated with it are extensively studied, little is known about the initiation of the aging process. Telomerase is down-regulated early in embryonic differentiation, thereby contributing to telomeric attrition and aging. The mechanisms underlying this inhibition remain elusive, but epigenetic studies in differentiating human embryonic stem (hES) cells could give clues about how and when DNA methylation and histone deacetylation work together to contribute to the inactivation of hTERT, the catalytic subunit of telomerase, at the onset of the aging process. We have confirmed the differentiation status of cultured hES colonies with morphological assessment and immunohistochemical stainings for pluripotent stem cells. In hES cells with varying degrees of differentiation, we have shown a stronger association between hES differentiation and expression of the epigenetic regulators DNMT3A and DNMT3B than between genetic modulators of differentiation such as c-MYC. We also propose a new model system for analyses of stem cell regions, which are differentially down-regulating the expression of hTERT and the actions of epigenetic modulators such as the DNMTs and histone methyltransferases. |
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Authors:
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Sharla M O Phipps; William K Love; Troy E Mott; Lucy G Andrews; Trygve O Tollefsbol |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-10-25 |
Journal Detail:
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Title: Molecular biotechnology Volume: 41 ISSN: 1073-6085 ISO Abbreviation: Mol. Biotechnol. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-01-21 Completed Date: 2009-08-03 Revised Date: 2010-12-17 |
Medline Journal Info:
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Nlm Unique ID: 9423533 Medline TA: Mol Biotechnol Country: United States |
Other Details:
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Languages: eng Pagination: 201-7 Citation Subset: IM |
Affiliation:
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Department of Biology, University of Alabama at Birmingham, 175 Campbell Hall, 1300 University Boulevard, Birmingham, AL 35294-1170, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging Alkaline Phosphatase / metabolism Animals Biological Markers / metabolism Cell Differentiation / genetics* Cells, Cultured DNA (Cytosine-5-)-Methyltransferase / metabolism Embryonic Stem Cells / cytology*, metabolism* Epigenesis, Genetic Fibroblasts / metabolism Fibronectins / metabolism Gene Expression Regulation* Histones / metabolism Humans Immunohistochemistry Methylation Mice Microscopy, Phase-Contrast Proto-Oncogene Proteins c-myc / metabolism Telomerase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA129415/CA/NCI NIH HHS; R01 CA129415-02/CA/NCI NIH HHS; R01 CA129415-04/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Fibronectins; 0/Histones; 0/Proto-Oncogene Proteins c-myc; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.7.7.49/Telomerase; EC 3.1.3.1/Alkaline Phosphatase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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