Expression data from mouse embryonic stem cells across a time course of Erk stimulation. Mus musculus

Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification we explore the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function experiments reveal a role for Erk signaling in suppressing endodermal differentiation, but not neural specification. Activation of Erk signaling in ESCs de-represses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming while sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation. We use microarray analysis to determine the transcription response to Erk1/2 in mouse embryonic stem cells across a 24 hour window of time Overall design: Mouse ESCs carrying a tamoxifen inducible constitutively active c-Raf fusion protein were stimulated for 6 time points (30minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours) in the presence of 250nM PD173074. Uninduced (0h hours) and DMSO only treated cells served as controls.