Figure 1

The transcription factor interaction circuit along with external factors influences. The core network for the mutual and self-regulatory interactions between NANOG, OCT4-SOX2 heterodimer, FGF4 and differentiation gene G. The dashed lines indicate the effect of external factors when cells are maintained in two different media, LIF+BMP4 and the 2i/3i respectively. The dynamical model is based upon the following (see Methods): OCT4-SOX2 induces NANOG. NANOG dimerizes and regulates itself positively. NANOG represses G, which regulates itself positively. OCT4-SOX2 induces G and the latter suppresses both NANOG and OCT4-SOX2. LIF induces NANOG through Klf4. OCT4-SOX2 induces FGF4, which suppresses NANOG. The 2i/3i medium suppresses FGF4.