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上皮间质转化(EMT)中的塑性和异质性的数学建模。

Mathematical Modeling of Plasticity and Heterogeneity in EMT.

机构信息

PhD Program in Systems, Synthetic, and Physical Biology, Rice University, Houston, TX, USA.

Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.

出版信息

Methods Mol Biol. 2021;2179:385-413. doi: 10.1007/978-1-0716-0779-4_28.

DOI:10.1007/978-1-0716-0779-4_28
PMID:32939734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8178376/
Abstract

The epithelial-mesenchymal transition (EMT) and the corresponding reverse process, mesenchymal-epithelial transition (MET), are dynamic and reversible cellular programs orchestrated by many changes at both biochemical and morphological levels. A recent surge in identifying the molecular mechanisms underlying EMT/MET has led to the development of various mathematical models that have contributed to our improved understanding of dynamics at single-cell and population levels: (a) multi-stability-how many phenotypes can cells attain during an EMT/MET?, (b) reversibility/irreversibility-what time and/or concentration of an EMT inducer marks the "tipping point" when cells induced to undergo EMT cannot revert?, (c) symmetry in EMT/MET-do cells take the same path when reverting as they took during the induction of EMT?, and (d) non-cell autonomous mechanisms-how does a cell undergoing EMT alter the tendency of its neighbors to undergo EMT? These dynamical traits may facilitate a heterogenous response within a cell population undergoing EMT/MET. Here, we present a few examples of designing different mathematical models that can contribute to decoding EMT/MET dynamics.

摘要

上皮-间充质转化 (EMT) 和相应的逆向过程,间充质-上皮转化 (MET),是由生化和形态水平的许多变化协调的动态和可逆的细胞程序。最近,在确定 EMT/MET 背后的分子机制方面取得了很大进展,这导致了各种数学模型的发展,这些模型有助于我们更好地理解单细胞和群体水平的动力学:(a) 多稳定性-在 EMT/MET 过程中,细胞可以获得多少种表型?(b) 可逆性/不可逆性-细胞诱导 EMT 时,需要多少 EMT 诱导剂的时间和/或浓度才能达到“临界点”,此时细胞不能逆转?(c) EMT/MET 中的对称性-细胞在逆转时是否会沿着与诱导 EMT 时相同的路径前进?(d) 非细胞自主机制-正在经历 EMT 的细胞如何改变其邻居经历 EMT 的倾向?这些动态特征可能有助于 EMT/MET 过程中细胞群体的异质反应。在这里,我们介绍了一些设计不同数学模型的例子,这些模型可以有助于解码 EMT/MET 动力学。

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本文引用的文献

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A mechanism for epithelial-mesenchymal heterogeneity in a population of cancer cells.一种癌细胞群体中上皮-间充质异质性的机制。
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Mapping lung cancer epithelial-mesenchymal transition states and trajectories with single-cell resolution.单细胞分辨率绘制肺癌上皮-间充质转化状态和轨迹。
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Biophysics at the coffee shop: lessons learned working with George Oster.在咖啡店的生物物理学:与乔治·奥斯特合作的经验教训。
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Interconnected feedback loops among ESRP1, HAS2, and CD44 regulate epithelial-mesenchymal plasticity in cancer.ESRP1、HAS2和CD44之间相互关联的反馈回路调节癌症中的上皮-间质可塑性。
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Context-dependent EMT programs in cancer metastasis.癌症转移中 EMT 程序的上下文相关性。
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Acquisition of a hybrid E/M state is essential for tumorigenicity of basal breast cancer cells.获得杂交 E/M 状态对于基底乳腺癌细胞的致瘤性至关重要。
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