Faculty of Biological Sciences and Frankfurt Institute for Advanced Studies (FIAS), Goethe Universität Frankfurt am Main, Ruth-Moufang-Straße 1, 60438, Frankfurt, Germany.
Faculty of Biological Sciences and Buchmann Institute for Molecular Life Sciences (BMLS), Goethe Universität Frankfurt am Main, Max-von-Laue Str. 15, 60438, Frankfurt, Germany.
Sci Rep. 2020 Dec 29;10(1):22405. doi: 10.1038/s41598-020-80141-3.
During the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell-cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.
在哺乳动物的着床前阶段，细胞经历两个后续的细胞命运决定。在第一个决定中，滋养外胚层和内细胞团形成。随后，内细胞团分离为上胚层和原始内胚层。内细胞团类器官代表了一种实验模型系统，模拟了第二次细胞命运决定。已经表明，相同命运的细胞比随机细胞命运决定更倾向于聚类。有三个主要过程被假设为对细胞命运排列做出贡献：（1）化学信号；（2）细胞分选；（3）细胞增殖。为了量化细胞增殖对观察到的细胞谱系类型聚类的影响，我们开发了一个基于代理的模型，该模型考虑了机械细胞-细胞相互作用，即粘附和排斥、细胞分裂、随机细胞命运决定和细胞命运遗传。该模型支持这样的假设，即初始细胞命运获得是一个随机驱动的过程，发生在内细胞团类器官的早期发育过程中。此外，我们表明，在细胞分裂过程中，仅由于细胞命运遗传就可以出现观察到的邻域结构。
