Id1 stabilises epiblast identity by sensing delays in nodal activation and adjusting the timing of differentiation

Controlling responsiveness to prevailing signals is critical for robust transitions between cell states during development. For example, FGF drives naïve pluripotent cells into extraembryonic lineages before implantation but sustains pluripotency in primed cells of the post-implantation epiblast. Nanog supports pluripotency in naïve cells while Nodal supports pluripotency in primed cells, but the handover from Nanog to Nodal does not proceed seamlessly, opening up the risk of aberrant differentiation if FGF is activated before Nodal. Here we report that Id1 acts as a sensor to detect delays in Nodal activation after downregulation of Nanog. Id1 then suppresses FGF activity to delay differentiation. Accordingly, Id1 is not required for naïve or primed pluripotency but rather stabilises epiblast identity during the transition between these states. These findings help explain how development proceeds robustly in the face of imprecise signals, and highlight the importance of mechanisms that stabilise cell identity during developmental transitions.