Emergent dynamics of thymocyte development and lineage determination.
Emergent dynamics of thymocyte development and lineage determination.
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DOI：
10.1371/journal.pcbi.0030013
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发表时间：
2007-01-26
影响因子：
4.3
通讯作者：
Cohen IR
中科院分区：
文献类型：
--
作者：
Efroni S;Harel D;Cohen IR
实验产生了大量关于胸腺细胞发育过程中涉及的基因、分子和细胞的数据。在这里，我们使用计算机驱动的模拟，利用胸腺细胞发育的数据来生成一个集成的动态表示-一种我们称之为反应性动画（RA）的新技术。RA揭示了复杂动态生物系统中的涌现特性。我们通过复制和扩展已知基因敲除的作用，将RA应用于胸腺细胞发育：CXCR4和CCR9。RA模拟揭示了胸腺细胞竞争在主要组织相容性复合体呈现中的作用。我们现在报道，这种竞争是正常解剖区室化所必需的，可以影响趋化因子梯度内胸腺细胞速度的速率，并且可以解释从双阳性前体发育而来的单阳性CD4和CD8谱系之间的不比例。生物系统是复杂性的体现，这是直觉无法理解的。生物学家已经积累了大量关于组成生命系统的分子、细胞和离散相互作用的数据，但单凭这些事实并不能解释这些系统是如何动态工作的。我们开发了一种混合的计算方法来模拟复杂系统，称为反应动画（RA）。RA使用自下而上的多种实验数据集成来创建系统中相互作用的细胞和分子的集成和动态表示。RA忠实于实验事实，同时它以动画的形式呈现动作，直接进入眼睛和大脑。最重要的是，RA是分析性的、交互式的，并且允许在计算机上进行实验。在这里，我们使用RA揭示胸腺细胞发育的意外涌现特性。特别是，我们现在报道，胸腺细胞之间的刺激位点竞争可能在产生胸腺精细解剖，选择具有一定迁移速度范围的胸腺细胞以及解释CD4与CD8 T细胞谱系比率的悖论中发挥重要作用。本研究强调了对复杂数据集的动画交互模拟所提供的解释力和对实验的潜在帮助。
Experiments have generated a plethora of data about the genes, molecules, and cells involved in thymocyte development. Here, we use a computer-driven simulation that uses data about thymocyte development to generate an integrated dynamic representation—a novel technology we have termed reactive animation (RA). RA reveals emergent properties in complex dynamic biological systems. We apply RA to thymocyte development by reproducing and extending the effects of known gene knockouts: CXCR4 and CCR9. RA simulation revealed a previously unidentified role of thymocyte competition for major histocompatability complex presentation. We now report that such competition is required for normal anatomical compartmentalization, can influence the rate of thymocyte velocities within chemokine gradients, and can account for the disproportion between single-positive CD4 and CD8 lineages developing from double-positive precursors. Biological systems are the embodiment of complexity that defies intuitive understanding. Biologists have accumulated masses of data about the molecules, cells, and discrete interactions that compose living systems, but the list of facts alone cannot explain how such systems work dynamically. We have developed a hybrid, computational approach to the simulation of complex systems called reactive animation (RA). RA uses a bottom-up integration of diverse experimental data to create an integrated and dynamic representation of the system's interacting cells and molecules. RA is faithful to experimental fact, while it plays out the action in animated formats directly accessible to the eye and mind. Most importantly, RA is analytical, interactive, and allows experimentation in silico. Here, we use RA to reveal unexpected emergent properties of thymocyte development. In particular, we now report that competition between thymocytes for sites of stimulation could be important in generating the fine anatomy of the thymus, in selecting for thymocytes with a range of migration velocities, and in explaining the paradox of CD4 to CD8 T cell lineage ratios. This study highlights the explanatory power and the potential aid to experimentation offered by an animated, interactive simulation of complex sets of data.
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影响因子：
4.3
作者：
Meier-Schellersheim M;Xu X;Angermann B;Kunkel EJ;Jin T;Germain RN
通讯作者：
Germain RN
影响因子：
2.2
作者：
Efroni, S;Harel, D;Cohen, IR
通讯作者：
Cohen, IR
DOI：
10.1084/jem.20030170
发表时间：
2003-06-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bosselut R;Guinter TI;Sharrow SO;Singer A
通讯作者：
Singer A
影响因子：
4.4
作者：
Plotkin, J;Prockop, SE;Petrie, HT
通讯作者：
Petrie, HT
影响因子：
7
作者：
Efroni, S;Harel, D;Cohen, LR
通讯作者：
Cohen, LR