人多能干细胞胞内OCT4调控的数学模型框架
A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells
摘要：
人类多能干细胞（hPSC）在再生医学，药物发现和个性化医学中具有很好的临床应用前景，因为它们有分化成所有细胞类型的潜力，这种特性称为多能性。需要更深入地了解多能性是如何调节的，以帮助实验控制多能性和分化轨迹。数学建模提供了一种非侵入性的工具，通过它来探索、验证和复制多能性的调节以及对细胞命运的影响。在这里，我们使用多能性转录因子OCT 4在生长的hPSC集落中表达的实验数据来开发和评估用于时间多能性调节的数学模型。我们考虑分数布朗运动和随机逻辑方程，并探讨加性和乘性噪声的影响。我们说明了使用时间依赖性的承载能力和引进Allee效应的随机逻辑方程来描述细胞分化。这种用于描述细胞内OCT 4调节的数学框架可以扩展到其他转录因子，并发展成复杂的预测模型。
英文摘要：
Human pluripotent stem cells (hPSCs) have promising clinical applications in regenerative medicine, drug-discovery and personalised medicine due to their potential to differentiate into all cell types, a property know as pluripotency. A deeper understanding of how pluripotency is regulated is required to assist in controlling pluripotency and differentiation trajectories experimentally. Mathematical modelling provides a non-invasive tool through which to explore, characterise and replicate the regulation of pluripotency and the consequences on cell fate. Here we use experimental data of the expression of the pluripotency transcription factor OCT4 in a growing hPSC colony to develop and evaluate mathematical models for temporal pluripotency regulation. We consider fractional Brownian motion and the stochastic logistic equation and explore the effects of both additive and multiplicative noise. We illustrate the use of time-dependent carrying capacities and the introduction of Allee effects to the stochastic logistic equation to describe cell differentiation. This mathematical framework for describing intra-cellular OCT4 regulation can be extended to other transcription factors and developed into sophisticated predictive models.
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