Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Biophys J. 2012 Nov 7;103(9):2011-20. doi: 10.1016/j.bpj.2012.08.062.
Cell fusion, a process that merges two or more cells into one, is required for normal development and has been explored as a tool for stem cell therapy. It has also been proposed that cell fusion causes cancer and contributes to its progression. These functions rely on a poorly understood ability of cell fusion to create new cell types. We suggest that this ability can be understood by considering cells as attractor networks whose basic property is to adopt a set of distinct, stable, self-maintaining states called attractors. According to this view, fusion of two cell types is a collision of two networks that have adopted distinct attractors. To learn how these networks reach a consensus, we model cell fusion computationally. To do so, we simulate patterns of gene activities using a formalism developed to simulate patterns of memory in neural networks. We find that the hybrid networks can assume attractors that are unrelated to parental attractors, implying that cell fusion can create new cell types by nearly instantaneously moving cells between attractors. We also show that hybrid networks are prone to assume spurious attractors, which are emergent and sporadic network states. This finding means that cell fusion can produce abnormal cell types, including cancerous types, by placing cells into normally inaccessible spurious states. Finally, we suggest that the problem of colliding networks has general significance in many processes represented by attractor networks, including biological, social, and political phenomena.
细胞融合,即将两个或多个细胞合并为一个的过程,是正常发育所必需的,并且已被探索作为干细胞治疗的工具。也有人提出细胞融合会导致癌症,并促进其进展。这些功能依赖于细胞融合形成新细胞类型的能力,而这种能力目前还了解甚少。我们认为,可以通过将细胞视为吸引子网络来理解这种能力,其基本属性是采用一组独特的、稳定的、自我维持的状态,称为吸引子。根据这一观点,两种细胞类型的融合是两个已经采用不同吸引子的网络的碰撞。为了了解这些网络如何达成共识,我们从计算角度对细胞融合进行建模。为此,我们使用一种形式化方法模拟基因活动模式,该方法用于模拟神经网络中的记忆模式。我们发现,杂交网络可以采用与亲本吸引子无关的吸引子,这意味着细胞融合可以通过在吸引子之间几乎瞬间移动细胞来创建新的细胞类型。我们还表明,杂交网络容易采用虚假吸引子,即突发和偶然的网络状态。这一发现意味着,通过将细胞置于通常无法进入的虚假状态,细胞融合可以产生异常的细胞类型,包括癌变类型。最后,我们提出,在许多由吸引子网络表示的过程中,包括生物、社会和政治现象,碰撞网络的问题具有普遍意义。