Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development.
Dev Cell
; 11(4): 535-46, 2006 Oct.
Article
em En
| MEDLINE
| ID: mdl-17011492
ABSTRACT
The transcriptional mechanisms underlying lineage specification and differentiation of embryonic stem (ES) cells remain elusive. Oct-3/4 (POU5f1) is one of the earliest transcription factors expressed in the embryo. Both the pluripotency and the fate of ES cells depend upon a tight control of Oct-3/4 expression. We report that transgene- or TGFbeta-induced increase in Oct-3/4 mRNA and protein levels in undifferentiated ES cells and at early stages of differentiation triggers expression of mesodermal and cardiac specific genes through Smad2/4. cDNA antisense- and siRNA-mediated inhibition of upregulation of Oct-3/4 in ES cells prevent their specification toward the mesoderm and their differentiation into cardiomyocytes. Similarly, Oct-3/4 siRNA injected in the inner cell mass of blastocysts impairs cardiogenesis in early embryos. Thus, quantitative Oct-3/4 expression is regulated by a morphogen, pointing to a pivotal and physiological function of the POU factor in mesodermal and cardiac commitments of ES cells and of the epiblast.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Regulação da Expressão Gênica no Desenvolvimento
/
Miócitos Cardíacos
/
Fator 3 de Transcrição de Octâmero
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Coração
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article