Phenotypic variability, not noise, accounts for most of the cell-to-cell heterogeneity in IFN-γ and oncostatin M signaling responses

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Phenotypic variability, not noise, accounts for most of the cell-to-cell heterogeneity in IFN-γ and oncostatin M signaling responses
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Why do cells vary in their signaling responses? Using a binucleated cell system, a new study in SciSignal finds that molecular variability across cells—and not random biochemical “noise”—may shape variations in signaling outcomes. SystemsBiology

The same signaling stimulus can induce variable outcomes among the same cell type in a group of cells or tissue, prompting the notion that signaling is influenced by random biochemical reactions, or molecular “noise.” Topolewski. generated multinuclear fibroblasts to explore whether heterogeneity in the cellular response to cytokines was the result of stochastic noise in the system or of cell-to-cell variability in molecular content.

Alternatively, heterogeneity could arise from differences in molecular content between cells, termed molecular phenotypic variability, which does not necessarily imply imprecise signaling. The contribution of these two processes to signaling heterogeneity is unclear. Here, we fused fibroblasts to produce binuclear syncytia to distinguish noise from phenotypic variability in the analysis of cytokine signaling.

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