Population robustness arising from cellular heterogeneity.

ABSTRACT: Heterogeneity between individual cells is a common feature of dynamic cellular processes, including signaling, transcription, and cell fate; yet the overall tissue level physiological phenotype needs to be carefully controlled to avoid fluctuations. Here we show that in the NF-kappaB signaling system, the precise timing of a dual-delayed negative feedback motif [involving stochastic transcription of inhibitor kappaB (IkappaB)-alpha and -epsilon] is optimized to induce heterogeneous timing of NF-kappaB oscillations between individual cells. We suggest that this dual-delayed negative feedback motif enables NF-kappaB signaling to generate robust single cell oscillations by reducing sensitivity to key parameter perturbations. Simultaneously, enhanced cell heterogeneity may represent a mechanis

SUBMITTER: Paszek P 

PROVIDER: S-EPMC2895068 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature