Driving pluripotency and reprogramming: Nuclear receptors at the helm

•Detailed examples of orphan nuclear receptors in pluripotency and reprogramming.•Functions of nuclear receptors in retinoic acid signalling in pluripotency.•Involvement of nuclear receptors in the exit from pluripotency.

The identity of a cell is determined by the concerted interplay of multiple molecular modulators such as transcription factors, chromatin modifiers and signalling mediators. Among these, the transcriptional circuitry holds great influence on the specification and maintenance of a cellular state, and its perturbation can trigger a transition to another cell state. This is particularly striking in the field of pluripotency, where tempering the expression levels of one or few transcription factors is sufficient to induce the loss or acquisition of the pluripotent state. Recently, nuclear receptors, a class of transcription factors, have emerged as major players in the molecular network governing pluripotency. In this review, we discuss the importance of nuclear receptors in embryonic stem cell self-renewal, differentiation and cellular reprogramming, highlighting recent discoveries as well as providing an outlook in stem cell and nuclear receptor research.