Fig. 1.

Signaling network heterogeneity in cell populations. A, Mutated signaling proteins (e.g., kinases) may cause genetic heterogeneity in a population of cells and leads to differential signaling networks. B, Non-genetic signaling network heterogeneity may origin from extrinsic factors including stimulus concentration, matrix stiffness, local crowdedness, oxygen and nutrient gradients, as well as the intrinsic noise. C, Signaling network heterogeneity results in phenotypical variances in a population of cells. Bulk analysis averages these variances, resulting in misinterpretation of cell signaling network behaviors and cell phenotypes.