Dynamical Reorganization of Transcriptional Events Governs Robust Nanog Heterogeneity

Nanog maintains the pluripotency of embryonic stem cells (ESCs), while demonstrating high expression heterogeneity. Intriguingly, the overall heterogeneity at the Nanog mRNA level under various culture conditions gets precisely partitioned into intrinsic and extrinsic fluctuations. However, the dynamical origin of such a robust transcriptional noise regulation still remains illusive. Herein, we propose a new stochastic simulation strategy that efficiently reconciles the strict apportioning of fluctuations observed in Nanog transcription, while predicting possible experimental scenarios to avoid such an exact noise segregation. Importantly, our model analyses reveal that different culture conditions essentially preserve the robust Nanog expression heterogeneity by altering the dynamics of transcriptional events. In the future, these insights will be useful to systematically maneuver cell-fate decision-making events of ESCs.