Oct-3/4 Dose Dependently Regulates Specification of Embryonic Stem Cells toward a Cardiac Lineage and Early Heart Development

Dana Zeineddine, Evangelia Papadimou, Karim Chebli, Mathieu Gineste, Jun Liu, Corinne Grey, Sherry Thurig, Atta Behfar, Valerie A A. Wallace, Ilona S. Skerjanc, Michel Pucéat

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

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 TGFβ-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.

Original languageEnglish (US)
Pages (from-to)535-546
Number of pages12
JournalDevelopmental Cell
Volume11
Issue number4
DOIs
StatePublished - Oct 2006

Keywords

  • DEVBIO
  • STEMCELL

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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