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干细胞与发育系统的计算机模拟模型。

In-silico models of stem cell and developmental systems.

作者信息

Setty Yaki

机构信息

Computational Systems Biology, Max-Planck-Institut für Informatik, Saarbrücken 66123, Germany.

出版信息

Theor Biol Med Model. 2014 Jan 8;11:1. doi: 10.1186/1742-4682-11-1.

Abstract

Understanding how developmental systems evolve over time is a key question in stem cell and developmental biology research. However, due to hurdles of existing experimental techniques, our understanding of these systems as a whole remains partial and coarse. In recent years, we have been constructing in-silico models that synthesize experimental knowledge using software engineering tools. Our approach integrates known isolated mechanisms with simplified assumptions where the knowledge is limited. This has proven to be a powerful, yet underutilized, tool to analyze the developmental process. The models provide a means to study development in-silico by altering the model's specifications, and thereby predict unforeseen phenomena to guide future experimental trials. To date, three organs from diverse evolutionary organisms have been modeled: the mouse pancreas, the C. elegans gonad, and partial rodent brain development. Analysis and execution of the models recapitulated the development of the organs, anticipated known experimental results and gave rise to novel testable predictions. Some of these results had already been validated experimentally. In this paper, I review our efforts in realistic in-silico modeling of stem cell research and developmental biology and discuss achievements and challenges. I envision that in the future, in-silico models as presented in this paper would become a common and useful technique for research in developmental biology and related research fields, particularly regenerative medicine, tissue engineering and cancer therapeutics.

摘要

了解发育系统如何随时间演变是干细胞和发育生物学研究中的一个关键问题。然而,由于现有实验技术的障碍,我们对这些系统的整体理解仍然是片面和粗略的。近年来,我们一直在构建计算机模拟模型,利用软件工程工具整合实验知识。我们的方法将已知的孤立机制与知识有限时的简化假设相结合。事实证明,这是一种强大但未得到充分利用的分析发育过程的工具。这些模型提供了一种通过改变模型规格在计算机上研究发育的方法,从而预测不可预见的现象以指导未来的实验试验。迄今为止,已经对来自不同进化生物体的三个器官进行了建模:小鼠胰腺、秀丽隐杆线虫性腺和部分啮齿动物大脑发育。对模型的分析和执行概括了器官的发育过程,预测了已知的实验结果,并产生了新的可测试预测。其中一些结果已经通过实验得到验证。在本文中,我回顾了我们在干细胞研究和发育生物学的逼真计算机模拟建模方面所做的努力,并讨论了取得的成就和面临的挑战。我设想,在未来,本文中介绍的计算机模拟模型将成为发育生物学及相关研究领域,特别是再生医学、组织工程和癌症治疗研究中一种常用且有用的技术。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4916/3896968/5ac8102edf10/1742-4682-11-1-1.jpg

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