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在细胞 Potts 框架中编程基于并列细胞信号的合成信号网络。

Programming Juxtacrine-Based Synthetic Signaling Networks in a Cellular Potts Framework.

机构信息

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

The Eli and Edythe Broad CIRM Center, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

出版信息

Methods Mol Biol. 2024;2760:283-307. doi: 10.1007/978-1-0716-3658-9_17.

Abstract

Synthetic development is a synthetic biology subfield aiming to reprogram higher-order eukaryotic cells for tissue formation and morphogenesis. Reprogramming efforts commonly rely upon implementing custom signaling networks into these cells, but the efficient design of these signaling networks is a substantial challenge. It is difficult to predict the tissue/morphogenic outcome of these networks, and in vitro testing of many networks is both costly and time-consuming. We therefore developed a computational framework with an in silico cell line (ISCL) that sports basic but modifiable features such as adhesion, motility, growth, and division. More importantly, ISCL can be quickly engineered with custom genetic circuits to test, improve, and explore different signaling network designs. We implemented this framework in a free cellular Potts modeling software CompuCell3D. In this chapter, we briefly discuss how to start with CompuCell3D and then go through the steps of how to make and modify ISCL. We then go through the steps of programming custom genetic circuits into ISCL to generate an example signaling network.

摘要

合成开发是合成生物学的一个分支,旨在重新编程高等真核细胞以进行组织形成和形态发生。重新编程工作通常依赖于将定制的信号网络引入这些细胞中,但这些信号网络的高效设计是一个重大挑战。很难预测这些网络的组织/形态发生结果,并且许多网络的体外测试既昂贵又耗时。因此,我们开发了一个具有计算细胞系(ISCL)的计算框架,该细胞系具有基本但可修改的特征,如粘附、运动、生长和分裂。更重要的是,ISCL 可以使用定制的遗传电路快速设计,以测试、改进和探索不同的信号网络设计。我们在免费的细胞 Potts 建模软件 CompuCell3D 中实现了这个框架。在这一章中,我们简要讨论了如何从 CompuCell3D 开始,然后逐步介绍如何制作和修改 ISCL。然后,我们将逐步介绍如何将定制的遗传电路编程到 ISCL 中以生成示例信号网络。

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