HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion.
Biochem Biophys Res Commun
; 355(2): 331-7, 2007 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-17300753
ABSTRACT
To examine the mechanism by which growth-stimulated pancreatic beta-cells dedifferentiate, somatic cell fusions were performed between MIN6, a highly differentiated mouse insulinoma, and betalox5, a cell line derived from human beta-cells which progressively dedifferentiated in culture. MIN6/betalox5 somatic cells hybrids underwent silencing of insulin expression and a marked decline in PDX1, NeuroD, and MafA, indicating that betalox5 expresses a dominant transacting factor(s) that represses beta-cell differentiation. Expression of Hes1, which inhibits endocrine differentiation was higher in hybrid cells than in parental MIN6 cells. Hes6, a repressor of Hes1, was highly expressed in primary beta-cells as well as MIN6, but was repressed in hybrids. Hes6 overexpression using a retroviral vector led to a decrease in Hes1 levels, an increase in beta-cell transcription factors and partial restoration of insulin expression. We conclude that the balance of Notch activators and inhibitors may play an important role in maintaining the beta-cell differentiated state.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Fusão Celular
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Núcleo Celular
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Ilhotas Pancreáticas
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Insulina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos