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Epigenetic Regulation of Nestin Expression during Neurogenic Differentiation of Adipose Tissue Stem Cells.
MedLine Citation:
PMID:  23140086     Owner:  NLM     Status:  Publisher    
Adipose tissue-derived stem cells (ASCs) have received considerable attention due to their easy access, expansion potential and differentiation capacity. ASCs are believed to have the potential to differentiate into neurons. However, the mechanisms by which this may occur remain largely unknown. Here, we show that culturing ASCs under active proliferation greatly improves their propensity to differentiate towards osteogenic, adipogenic and neurogenic lineages. Neurogenic-induced ASCs express early neurogenic genes as well as markers of mature neurons including voltage-gated ion channels. Nestin, highly expressed in neural progenitors, is upregulated by mitogenic stimulation of ASCs, and as in neural progenitors, then repressed during neurogenic differentiation. Nestin gene (NES) expression under these conditions appears to be regulated by epigenetic mechanisms. The neural-specific, but not muscle-specific, enhancer regions of NES are CpG demethylated by mitogenic stimulation, and re-methylated upon neurogenic differentiation. We observe dynamic changes in histone H3K4, H3K9 and H3K27 methylation on the NES locus before and during neurogenic differentiation that are consistent with epigenetic processes involved in the regulation of NES expression. We suggest that ASCs are epigenetically 'pre-patterned' to differentiate toward a neural lineage and that this pre-patterning is enhanced by demethylation of critical NES enhancer elements upon mitogenic stimulation preceding neurogenic differentiation. Our findings provide molecular evidence that the differentiation repertoire of ASCs may extend beyond mesodermal lineages.
Jean-Luc Boulland; Maria Mastrangelopoulou; Andrew C Boquest; Rune B Jakobsen; Agate Noer; Joel C Glover; Philippe Collas
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Stem cells and development     Volume:  -     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Institute of Basic Medical Sciences, Department of Physiology, P.O. Box 1103 - Blindern, Oslo, Norway, 0317, (+47) 22851205, (+47) 22851278;
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