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一个计算模型,用于研究干细胞在存在随机性的情况下维持组织内稳态和组织架构的决策机制。

A computational model of stem cells' decision-making mechanism to maintain tissue homeostasis and organization in the presence of stochasticity.

机构信息

School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.

National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

出版信息

Sci Rep. 2022 Jun 2;12(1):9167. doi: 10.1038/s41598-022-12717-0.

Abstract

The maintenance of multi-cellular developed tissue depends on the proper cell production rate to replace the cells destroyed by the programmed process of cell death. The stem cell is the main source of producing cells in a developed normal tissue. It makes the stem cell the lead role in the scene of a fully formed developed tissue to fulfill its proper functionality. By focusing on the impact of stochasticity, here, we propose a computational model to reveal the internal mechanism of a stem cell, which generates the right proportion of different types of specialized cells, distribute them into their right position, and in the presence of intercellular reactions, maintain the organized structure in a homeostatic state. The result demonstrates that the spatial pattern could be harassed by the population geometries. Besides, it clearly shows that our model with progenitor cells able to recover the stem cell presence could retrieve the initial pattern appropriately in the case of injury. One of the fascinating outcomes of this project is demonstrating the contradictory roles of stochasticity. It breaks the proper boundaries of the initial spatial pattern in the population. While, on the flip side of the coin, it is the exact factor that provides the demanded non-genetic diversity in the tissue. The remarkable characteristic of the introduced model as the stem cells' internal mechanism is that it could control the overall behavior of the population without need for any external factors.

摘要

多细胞组织的维持依赖于适当的细胞产生率,以替代程序性细胞死亡过程中破坏的细胞。干细胞是发育正常组织中产生细胞的主要来源。它使干细胞在完全形成的发育组织中扮演主导角色,以发挥其正常功能。通过关注随机性的影响,我们在这里提出了一个计算模型,以揭示干细胞的内部机制,该机制产生适当比例的不同类型的特化细胞,将它们分配到正确的位置,并在细胞间反应存在的情况下,维持组织在稳态下的有组织结构。结果表明,空间模式可能会受到种群几何形状的干扰。此外,它清楚地表明,我们的模型中具有能够恢复干细胞存在的祖细胞,可以在损伤的情况下适当地恢复初始模式。该项目的一个引人注目的结果是展示了随机性的矛盾作用。它打破了群体中初始空间模式的适当界限。而另一方面,它正是在组织中提供所需非遗传多样性的因素。所提出的模型作为干细胞内部机制的显著特征是,它可以控制群体的整体行为,而不需要任何外部因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1736/9163052/401d3cf0bf08/41598_2022_12717_Fig1_HTML.jpg

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