Data from: Cell-specific responses to the cytokine TGFβ are determined by variability in protein levels

The cytokine TGFβ provides important information during embryonic
development, adult tissue homeostasis and regeneration. Alterations in the
cellular response to TGFβ are involved in severe human diseases. To
understand how cells encode the extracellular input and transmit its
information to elicit appropriate responses, we acquired quantitative
time-resolved measurements of pathway activation at the single cell level.
We established dynamic time warping to quantitatively compare signaling
dynamics of thousands of individual cells and described heterogeneous
single-cell responses by mathematical modeling. Our combined experimental
and theoretical study revealed that the response to a given dose of TGFβ
is determined cell-specifically by the levels of defined signaling
proteins. This heterogeneity in signaling protein expression leads to
decomposition of cells into classes with qualitatively distinct signaling
dynamics and phenotypic outcome. Negative feedback regulators promote
heterogeneous signaling, as a SMAD7 knock-out specifically affected the
signal duration in a subpopulation of cells. Taken together, we propose a
quantitative framework that allows predicting and testing sources of
cellular signaling heterogeneity.