The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells.
Cell
; 138(3): 449-62, 2009 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-19665969
ABSTRACT
We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed alpha cells fail to correct the hypoglucagonemia since they subsequently acquire a beta cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pâncreas
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Células-Tronco
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Diferenciação Celular
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Proteínas de Homeodomínio
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Células Secretoras de Glucagon
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Células Secretoras de Insulina
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Fatores de Transcrição Box Pareados
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha