The Problem of Colliding Networks and its Relation to Cell Fusion and Cancer

Abstract

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.

The shock of being united and symphiliosis

“…48 according to the colliding networks model, 44 these analogies may be even deeper than they seem. the model is based on the notion that gene expression patterns correspond to points in the waddington epigenetic landscape (sketched with the gray line), with the stable patterns (cell types) corresponding to the "valleys" known as attractors.…”

“…44,[51][52][53][54][55][56][57][58][59] Such commonality suggests that these features Figure 1. the pathways to tetraploidy in the evolution of species and somatic cells.…”

“…Several aspects of this process have been named the genomic 36 or transcriptome 40 shock, a conflict zone, 43 parental squabbles, 48 nuclear reprogramming, 60 and the problem of colliding networks. 44 To acknowledge the existence of this process and to have a term to refer to it as a whole, I suggest calling it symphiliosis, from a Greek word for reconciliation, "συμϕιλίωση", and, accordingly, referring to all interrelated instabilities associated with symphiliosis, of which we probably know only some, as symphilial instability, or SIN. Hence, the defining features of allopolyploids are a result of symphiliosis rather than of the increase in ploidy per se.…”

“…62 The accidental fusion of different somatic cells, as it happens during viral infections, 63 is akin to the marriage of randomly and blindly selected strangers, with similarly unexpected consequences. 44 …”

“…The search for what the transcriptome shock is and how the merged regulatory gene expression networks reach a consensus is still in its infancy [41][42][43][44][45][46][47][48] (see Box 2).…”