Stem Cells Research Today is a free monthly online journal that collates and summarizes the latest research about Stem Cells, including details on research, transplants, therapy, benefits.

Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development.

Zeineddine D, Papadimou E, Chebli K, Gineste M, Liu J, Grey C, Thurig S, Behfar A, Wallace VA, Skerjanc IS, Pucéat M

CNRS FRE2593, CRBM, 34293 Montpellier, France.

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.

Published 2 October 2006 in Dev Cell, 11(4): 535-46.
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