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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Quantifying the Waddington landscape and biological paths for development and differentiation
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Quantifying the Waddington landscape and biological paths for development and differentiation

机译：量化Waddington的景观和发展与分化的生物路径

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摘要

We developed a theoretical framework to prove the existence and quantify the Waddington landscape as well as chreode-biological paths for development and differentiation. The cells can have states with the higher probability ones giving the different cell types. Different cell types correspond to different basins of attractions of the probability landscape. We study how the cells develop from undifferentiated cells to differentiated cells from landscape perspectives. We quantified the Waddington landscape through construction of underlying probability landscape for cell development. We show the developmental process proceeds as moving from undifferentiated to the differentiated basins of attractions. The barrier height of the basins of attractions correlates with the escape time that determines the stability of cell types. We show that the developmental process can be quantitatively described 'and uncovered by the biological paths on the quantified Waddington landscape from undifferentiated to the differentiated cells. We found the dynamics of the developmental process is controlled by a combination of the gradient and curl force on the landscape. The biological paths often do not follow the steepest descent path on the landscape. The landscape framework also quantifies the possibility of reverse differentiation process such as cell reprogram-ming from differentiated cells back to the original stem cell. We show that the biological path of reverse differentiation is irreversible and different from the one for differentiation process. We found that the developmental process described by the underlying landscape and the associated biological paths is relatively stable and robust against the influences of environmental perturbations.
机译：我们开发了一个理论框架来证明其存在并量化Waddington的景观以及发展和分化的编导生物学路径。单元可以具有给出不同单元类型的较高概率状态。不同的像元类型对应于概率景观的不同吸引力盆地。我们从景观角度研究了细胞如何从未分化的细胞发展为分化的细胞。我们通过构建潜在的细胞发展概率图来量化沃丁顿景观。我们显示了从未分化的景点向差异化的盆地发展的过程。吸引力盆地的屏障高度与逃逸时间相关，逃逸时间决定了细胞类型的稳定性。我们表明，发展过程可以定量地描述，并由量化的Waddington景观上从未分化的细胞到分化的细胞的生物学路径所揭示。我们发现发展过程的动力学是受景观上的梯度和卷曲力的共同控制的。生物路径通常不遵循景观上最陡峭的下降路径。景观框架还量化了反向分化过程的可能性，例如从分化的细胞重新编程回原始干细胞的细胞重编程。我们表明反向分化的生物学途径是不可逆的，并且不同于分化过程。我们发现，由潜在景观和相关生物路径描述的发展过程相对稳定，并且能够抵御环境扰动的影响。

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    Jin Wang; Kun Zhang; Li Xu; Erkang Wang;

  • 作者单位

    State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022,People's Republic of China,Department of Chemistry, Physics, and Applied Mathematics, State University of New York, Stony Brook, NY 11794-3400;

    State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022,People's Republic of China;

    State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022,People's Republic of China;

    State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022,People's Republic of China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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