Activation of retinoic acid receptor signaling coordinates lineage commitment of spontaneously differentiating mouse embryonic stem cells in embryoid bodies.
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.
Simandi
Zoltan
Z
Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Balint
Balint Laszlo
BL
Poliska
Szilard
S
Ruhl
Ralph
R
Nagy
Laszlo
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D053595:Embryonic Stem Cells; D016193:G1 Phase; D015870:Gene Expression; D051379:Mice; D018168:Receptors, Retinoic Acid; D012176:Retinoids / Q000494:pharmacology; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014212:Tretinoin