Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm.

We discovered a role for the transcription factor OTX2 in formation of mouse definitive endoderm (DE). We used RNAseq to measure changes in gene expression and identify OTX2-regulated genes during directed differentiation of EpiSCs to Primitive Streak (PS) intermediates and DE Mouse EpiSCs were converted to PS; DE1 (24hrs from PS) and DE2 (48hrs from PS) . OTX2 was depleted for 21hrs at induction of each stage by dTAG13 treatment and OTX2-dependent genes were identified by bulk RNAseq.