Fine-tuning Nanog expression heterogeneity by altering MicroRNA regulation

Nanog exhibits a robust heterogeneous expression pattern within a population of embryonic stem cells (ESCs) under varied culture conditions. However, an efficient way to fine-tune the Nanog expression heterogeneity remains elusive. Herein, by employing a stochastic modeling approach, we demonstrate that Nanog expression heterogeneity can be controlled by modulating the regulatory features of a Nanog transcript specific microRNA. We demonstrate how and why the extent of origin dependent fluctuations in Nanog expression level can be altered by varying either the binding efficiency of the microRNA-mRNA complex or the expression level of the respective microRNA. Moreover, our model makes experimentally feasible and insightful predictions to maneuver the Nanog expression heterogeneity explicitly to achieve cell-type specific differentiation of ESCs.