A liaison between intrinsic and extrinsic regulators of pluripotency

A pluripotent cell state is regulated by complex transcription factor network under the control of extrinsic signals, so that undifferentiated cells can readily commit to any cell lineages in response to appropriate stimuli. A number of recent studies using pluripotent stem cells in vitro have shown that maintenance of pluripotency can be achieved with different combinations of extrinsic factors, yet by activating common intrinsic regulators. Two papers in this issue of The EMBO Journal identified Tfcp2l1 (also known as Crtr-1 or Tcfcp2l1) as a factor on which activating and repressing stimuli for pluripotency converge. The results provide insight into how intrinsic pluripotency regulatory network is stably organized downstream of diverse inputs.