IFATS collection: Selenium induces improvement of stem cell behaviors in human adipose-tissue stromal cells via SAPK/JNK and stemness acting signals.
Stem Cells
; 26(10): 2724-34, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-18583539
ABSTRACT
In the present study, the potential of selenium to enhance stem cell behavior through improvement of human adipose tissue-derived stromal cells (ATSCs) and the associated molecular mechanism was evaluated. Selenium-induced improvement in stem cell behavior of human ATSCs caused expression of several genes, indicating downregulated mature cell marker proteins coupled with increased cell growth and telomerase activities after the overexpression of Rex1, Nanog, OCT4, SOX2, KLF4, and c-Myc. Also, selenium-treated ATSCs significantly downregulated p53 and p21 tumor suppressor gene products. Selenium induced active growth and growth enhanced by the activation of signal proteins in ATSCs via the inhibition of reactive oxygen species-mediated phospho-stress-activated protein kinase/c-Jun N-terminal protein kinase activation. The selenium-induced activation of extracellular regulated kinases 1/2 and Akt in ATSCs resulted in a subsequent induction of the expression of stemness transcription factors, particularly Rex1, Nanog, and Oct4, along with definitive demethylation on regulatory regions of Rex-1, Nanog, and Oct4. The results of our small interfering RNA knockdown experiment showed that Rex1 plays a major role in the proliferation of selenium-induced ATSCs. Selenium-treated ATSCs also exhibited more profound differentiation into mesodermal and neural lineages. We performed a direct comparison of gene expression profiles in control ATSCs and selenium-treated ATSCs and delineated specific members of important growth factor, signaling, cell adhesion, and transcription factor families. The observations of improved life span and multipotency of selenium-treated ATSCs clearly indicate that selenium-treated ATSCs represent an extraordinarily useful candidate cell source for tissue regeneration. Disclosure of potential conflicts of interest is found at the end of this article.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Selênio
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Células-Tronco
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Tecido Adiposo
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Células Estromais
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Quinases de Proteína Quinase Ativadas por Mitógeno
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Proteínas Quinases JNK Ativadas por Mitógeno
Limite:
Animals
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Humans
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Coréia do Sul