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Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies
Authors:Zoltan Simandi  Balint Laszlo Balint  Szilard Poliska  Laszlo Nagy
Affiliation:a Nuclear Hormone Receptor Research Laboratory, Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
b Laboratory of Nutritional Bioactivation and Bioanalysis, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
c Genomics and Apoptosis Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary
Abstract:Retinoid signaling has been implicated in embryonic stem cell differentiation. Here we present a systematic analysis of gene expression changes in mouse embryonic stem cells (mESCs), during their spontaneous differentiation into embryoid bodies and the effect of all-trans retinoic acid (ATRA) on this process. We show that retinoic acid is present in the serum and is sufficient to activate retinoid signaling at a basal level in undifferentiated mESCs. This signal disappears during embryoid body formation. However exogenously added ATRA resets the spontaneous differentiation programs in embryoid bodies and initiates a distinct genetic program. These data suggest that retinoid signaling not only promotes a particular pathway but also acts as a context dependent general coordinator of the differentiation states in embryonic stem cells.
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