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Cells rely on input from extracellular growth factors to control their proliferation during development and adult homeostasis. Such mitogenic inputs are transmitted through multiple signaling pathways that synergize to precisely regulate cell cycle entry and progression. Although the architecture of these signaling networks has been characterized in molecular detail, their relative contribution, especially at later cell cycle stages, remains largely unexplored. By combining quantitative time-resolved measurements of fluorescent reporters in untransformed human cells with targeted pharmacological inhibitors and statistical analysis, we quantify epidermal growth factor (EGF)-induced signal processing in individual cells over time and dissect the dynamic contribution of downstream pathways. We define signaling features that encode information about extracellular ligand concentrations and critical time windows for inducing cell cycle transitions. We show that both extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) activity are necessary for initial cell cycle entry, whereas only PI3K affects the duration of S phase at later stages of mitogenic signaling.

Hintergrund: Seit einigen Jahren werden auf Flüssigkristallen basierende Optiken für akkommodierende IOL’s in Betracht gezogen. Sie bieten die Möglichkeit einer Brechkraftänderung bei extrem geringem Energieverbrauch. Versuche auf der optischen Bank konnten zeigen, dass die[zum vollständigen Text gelangen Sie über die oben angegebene URL], 69. Tagung der Vereinigung Norddeutscher Augenärzte (VNDA)

Einleitung: Die Bestimmung von akkommodativ bedingten Geometrieveränderungen des Auges ist generell eine messtechnische Herausforderung. Als ein möglicher Ansatz wurde in dieser Studie der IOLMaster 700 (Carl Zeiss Meditec AG) verwendet, um altersabhängige Veränderungen während[zum vollständigen Text gelangen Sie über die oben angegebene URL], 69. Tagung der Vereinigung Norddeutscher Augenärzte (VNDA)

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.