Core signalling pathways maintaining human pluripotent stem cells (hPSCs).
The pluripotent state is inherently unstable and minor perturbations disrupting the balance within the signalling network may lead to the initiation of differentiation to either one of the three germ layers or to extraembryonic derivatives. As a consequence, the shown pathways may act both to promote stemness in one setting and differentiation in another, all depending on the microenvironmental context, as well as the subcellular localisation and signalling dynamics of individual pathway components. Note that several of the displayed effectors exist in multiple isoforms and are currently omitted for clarity, although there are cases in which two isoforms may have different or even opposing effects on PSC biology [143]. The red question mark is used to denote existing uncertainty about the ability of PI3K and WNT signalling to access the same GSK3 pool. Dashed lines are used to indicate indirect regulatory relationships. Positive regulation is shown in green and negative regulation in black.