表观遗传学作为癌症可塑性的介体。
Epigenetics as a mediator of plasticity in cancer.
机构信息
Center for Epigenetics, Johns Hopkins University Schools of Medicine, Biomedical Engineering, and Public Health, Baltimore, MD 21205, USA.
Yale Systems Biology Institute and Department of Biomedical Engineering, Yale University, West Haven, CT 06516, USA.
出版信息
Science. 2023 Feb 10;379(6632):eaaw3835. doi: 10.1126/science.aaw3835.
The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light of experiments showing nondeterministic outcomes of regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to epigenetic and gene regulation landscapes and the associated ideas of entropy and attractor states, illustrating how their definitions are both more precise and relevant to understanding cancer etiology and the plasticity of cancerous states. We address the interplay between different types of regulatory landscapes and how their changes underlie cancer progression. We also consider the roles of cellular aging and intrinsic and extrinsic stimuli in modulating cellular states and how landscape alterations can be quantitatively mapped onto phenotypic outcomes and thereby used in therapy development.
描述多能细胞潜在细胞命运的表观遗传景观的概念，最初由 Conrad Waddington 提出，随着表明调控过程的非确定性结果和用于量化随机性的数学方法的实验而发展。在这篇综述中，我们讨论了表观遗传和基因调控景观的现代方法以及与之相关的熵和吸引子状态的概念，说明它们的定义如何更加精确和有助于理解癌症病因和癌变状态的可塑性。我们探讨了不同类型的调控景观之间的相互作用以及它们的变化如何构成癌症进展的基础。我们还考虑了细胞衰老以及内在和外在刺激在调节细胞状态中的作用，以及如何将景观改变定量映射到表型结果上，并将其用于治疗方法的开发。
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