@article{ac93f184f2e74a61b29028e4755296ce,
title = "Oct-3/4 Dose Dependently Regulates Specification of Embryonic Stem Cells toward a Cardiac Lineage and Early Heart Development",
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.",
keywords = "DEVBIO, STEMCELL",
author = "Dana Zeineddine and Evangelia Papadimou and Karim Chebli and Mathieu Gineste and Jun Liu and Corinne Grey and Sherry Thurig and Atta Behfar and Wallace, {Valerie A A.} and Skerjanc, {Ilona S.} and Michel Puc{\'e}at",
note = "Funding Information: We thank Dr. P. Travo (CRBM, Montpellier) for skillful help in cell imaging, Dr. H. Scholer (University of Pennsylvania) for the kind gift of Oct-3/4 cDNA, Dr. Derynck (UCSF) for the generous gift of the Smad2SSMS and Smad3ΔSSVS cDNAs and discussions about the use of these mutants, Dr. Katherine Yutsey (Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center) for skillful examination of the embryo images, Dr. Gilles Divita (CRBM, CNRS, Montpellier) for the kind gift of the MPG gene delivery peptide, Drs. D. Mornet and G. Hugon (University Montpellier I, France) for the kind gift of the anti-β-MHC antibody, Dr. H. Niwa (Riken, Kobe, Japan) for the kind gift of the ZHTc6 cell line, Chantal Jacquet and Eric Jouffre in the animal house of the IGMM for breeding mice (CNRS, Montpellier), Patricia Cavalier (IGMM) for the histology of embryos, Drs. D. Umlauf and R. Feil (IGMM) for help in the ChIP assay and stimulating discussions, Dr. A. Terzic (Mayo Clinic, Rochester, MN) for his continuous encouragement, and Drs. N. Taylor (IGMM, Montpellier) and F. Aimond (CRBM, Montpellier) for critical reading of the manuscript. This study was funded by a grant (N°8849) from Association Fran{\c c}aise contre les myopathies (AFM) to M.P. E.P. was a fellow from the Marie Curie Mobility Programme of the European Community. A.B. was supported by the Ruth and Bruce Rappaport Program in Vascular Biology and Gene Delivery at the Mayo Foundation and by the Mayo MD/PhD Program. D.Z. was a fellow from the Fondation pour la Recherche M{\'e}dicale. M.P. is an INSERM established investigator. ",
year = "2006",
month = oct,
doi = "10.1016/j.devcel.2006.07.013",
language = "English (US)",
volume = "11",
pages = "535--546",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "4",
}