Developmental Cell
Volume 11, Issue 4, October 2006, Pages 535-546
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Article
Oct-3/4 Dose Dependently Regulates Specification of Embryonic Stem Cells toward a Cardiac Lineage and Early Heart Development

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Summary

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.

DEVBIO
STEMCELL

Cited by (0)

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Lab address: http://www.medicine.uottawa.ca/microbio/bmi/eng/skerjanc.htm

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Lab address: http://www.crbm.cnrs.fr/%7Epuceat/

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Present address: Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, 20133 Milano, Italy.

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Present address: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905.