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Disentangling pro-mitotic signaling during cell cycle progression using time-resolved single-cell imaging

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Item Type:Article
Title:Disentangling pro-mitotic signaling during cell cycle progression using time-resolved single-cell imaging
Creators Name:Benary, M. and Bohn, S. and Lüthen, M. and Nolis, I.K. and Blüthgen, N. and Loewer, A.
Abstract: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.
Keywords:Mitogenic Signaling, MAPK Pathway, PI3K Pathway, Signaling Dynamics, Single-Cell Analysis, Cell-Cycle, scRNA-Seq, Time-Lapse Microscopy, Information Theory
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:107514
Date:14 April 2020
Official Publication:https://doi.org/10.1016/j.celrep.2020.03.078
PubMed:View item in PubMed

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