Department of Chemistry , IIT Bombay , Powai, Mumbai ? 400076 , India.
J Phys Chem B. 2019 Jun 27;123(25):5246-5255. doi: 10.1021/acs.jpcb.9b03411. Epub 2019 Jun 18.
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.
Nanog 维持胚胎干细胞（ESC）的多能性，同时表现出高度的表达异质性。有趣的是，在各种培养条件下，Nanog mRNA 水平的整体异质性被精确地分为内在和外在波动。然而，这种强大的转录噪声调节的动力学起源仍然难以捉摸。在这里，我们提出了一种新的随机模拟策略，有效地协调了在 Nanog 转录中观察到的严格波动分配，同时预测了可能的实验方案以避免这种精确的噪声分离。重要的是，我们的模型分析表明，不同的培养条件通过改变转录事件的动力学，基本上保持了 Nanog 表达异质性的稳健性。将来，这些见解将有助于系统地操纵 ESC 的细胞命运决策事件。
