Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features
Fig 7
Kinetics of the peak retention of upstream signaling stratify late response of immediate early gene expression patterns in single cells.
(A) Scatter plot showing bivariate immediate early genes c-Fos and c-Jun expression levels in individual cells picked from same cell types (data from [20]). Expression levels (−ΔCt measured by realtime PCR) of 151 single cells are shown at 60 min after an induced hypertension stimulus (refer [20] for details of the experiment). Marginal histograms for 151 cells are shown at the top and right for c-Jun and c-Fos IEG, respectively. Four phenotypes were statistically determined from top 25 percentile and bottom 25 percentile of c-Fos and c-Jun expression distributions, respectively. Red corresponds to ‘high c-Fos and high c-Jun’ phenotype, cyan corresponds to ‘low c-Fos and high c-Jun’ phenotype, blue corresponds to ‘low c-Fos and low c-Jun’ phenotype, and orange ‘high c-Fos and low c-Jun’ phenotype. (B) Scatter plot of the feature-space for the first two dominant signaling features, τ2J and τ2E, distinctively separating four gene expression phenotypes, determined through similar statistics from model simulations. Note that the colors are same as that of the respective phenotypes defined in A. The first 250 cells in each phenotypic region were used in the analysis. The dotted lines in the plots are the classifiers estimated by the root, and the next significant branches of the decision tree in C. The gray region in the background corresponds to the variability in 100,000 cells, spanning the entire functional space of the signaling features. (C) Decision tree analysis to identify the key features and their conditionalities driving the downstream immediate early genes expression phenotypes as the categorizers of upstream features, for the cells in B. See Fig 5C for details.