Laboratoire de Physique Statistique, CNRS, Université P. et M. Curie, École Normale Supérieure, Paris, France.
Biophys J. 2012 Feb 8;102(3):417-26. doi: 10.1016/j.bpj.2011.11.4022. Epub 2012 Feb 7.
The acquisition of different fates by cells that are initially in the same state is central to development. Here, we investigate the possible structures of bistable genetic networks that can allow two identical cells to acquire different fates through cell-cell interactions. Cell-autonomous bistable networks have been previously sampled using an evolutionary algorithm. We extend this evolutionary procedure to take into account interactions between cells. We obtain a variety of simple bistable networks that we classify into major subtypes. Some have long been proposed in the context of lateral inhibition through the Notch-Delta pathway, some have been more recently considered and others appear to be new and based on mechanisms not previously considered. The results highlight the role of posttranscriptional interactions and particularly of protein complexation and sequestration, which can replace cooperativity in transcriptional interactions. Some bistable networks are entirely based on posttranscriptional interactions and the simplest of these is found to lead, upon a single parameter change, to oscillations in the two cells with opposite phases. We provide qualitative explanations as well as mathematical analyses of the dynamical behaviors of various created networks. The results should help to identify and understand genetic structures implicated in cell-cell interactions and differentiation.
细胞在最初状态相同的情况下获得不同命运，这是发育的核心。在这里，我们研究了允许两个相同细胞通过细胞间相互作用获得不同命运的双稳态遗传网络的可能结构。细胞自主双稳态网络以前曾使用进化算法进行过采样。我们将这个进化过程扩展到考虑细胞间的相互作用。我们得到了各种简单的双稳态网络，并将它们分为主要亚型。其中一些在 Notch-Delta 途径的侧向抑制背景下很早就被提出，一些则是最近才被考虑，还有一些则是新的，基于以前未被考虑的机制。结果突出了转录后相互作用的作用，特别是蛋白质复合物和隔离的作用，它们可以替代转录相互作用中的协同作用。一些双稳态网络完全基于转录后相互作用，最简单的双稳态网络在单个参数改变时导致两个细胞以相反相位振荡。我们提供了各种创建网络的动态行为的定性解释和数学分析。这些结果应该有助于识别和理解涉及细胞间相互作用和分化的遗传结构。
