Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation. (Articolo in rivista)

Type
Label
  • Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation. (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1093/nar/gks207 (literal)
Alternative label
  • Schneider L, d'Adda di Fagagna F. (2012)
    Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation.
    in Nucleic acids research
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Schneider L, d'Adda di Fagagna F. (literal)
Pagina inizio
  • 5332 (literal)
Pagina fine
  • 5342 (literal)
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  • http://nar.oxfordjournals.org/content/40/12/5332.long (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 40 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 11 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 12 (literal)
Note
  • ISI Web of Science (WOS) (literal)
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • IFOM Foundation, The FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan and Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Via Abbiategrasso 207, 27100 Pavia, Italy (literal)
Titolo
  • Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation. (literal)
Abstract
  • Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) is a halogenated nucleotide of low toxicity commonly used to monitor DNA replication. It is considered a valuable tool for in vitro and in vivo studies, including the detection of the small population of neural stem cells (NSC) in the mammalian brain. Here, we show that NSC grown in self-renewing conditions in vitro, when exposed to BrdU, lose the expression of stem cell markers like Nestin, Sox2 and Pax6 and undergo glial differentiation, strongly up-regulating the astrocytic marker GFAP. The onset of GFAP expression in BrdU exposed NSC was paralleled by a reduced expression of key DNA methyltransferases (DNMT) and a rapid loss of global DNA CpG methylation, as we determined by our specially developed analytic assay. Remarkably, a known DNA demethylating compound, 5-aza-2'-deoxycytidine (Decitabine), had similar effect on demethylation and differentiation of NSC. Since our key findings apply also to NSC derived from murine forebrain, our observations strongly suggest more caution in BrdU uses in stem cells research. We also propose that BrdU and its related substances may also open new opportunities for differentiation therapy in oncology. (literal)
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