Schematic representation of the cell signal transduction pathways that are involved in pluripotency of mouse and human ES cells. Mouse ES cells: LIF binds to LIFR and GP130 heterodimers, which results in the activation of STAT3 signalling and AKT signalling and subsequent activation of the downstream target genes Klf4 and Tbx3. BMP binds to heterodimers of the Type I and Type II receptors. As a result, three Smad transcription factors (one of which is Smad 4) trimerize and translocate to the nucleus where they activate the expression of Id genes. LIF and BMP signalling also results in the expression of other members of the pluripotency factor network (e.g. Sox2, Nanog and Pou5f1), but it is unclear if this is a direct or an indirect effect. Human ES cells: FGF binds to FGF-receptor homodimers, which leads to AKT signalling. In parallel, Activin or Nodal homodimers binds to heterodimers of the Type I and Type II receptors. As a result, three Smad transcription factors (one of which is Smad 4) trimerize and translocate to the nucleus. Cooperatively, FGF and Activin/Nodal maintain pluripotency of human ES cells. The question marks depict our lack of knowledge on how these cell signal transduction pathways act on the pluripotency factor network (dashed line) in human ES cells.