Disentangling Pro-mitotic Signaling during Cell Cycle Progression using Time-Resolved Single-Cell Imaging

• DOI: 10.1016/j.celrep.2020.03.078
• Publication Date: 2020-04-14T15:00:10Z
• Authors: Manuela Benary; Stefan Bohn; Mareen Lüthen; Ilias K. Nolis; Nils Blüthgen; Alexander Loewer
• Keywords: Live cell imaging

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 precisely regulate cell cycle entry progression. Although the architecture of these networks has been characterized in molecular detail, relative contribution, especially at later stages, remains largely unexplored. By combining quantitative time-resolved measurements fluorescent reporters untransformed human cells with targeted pharmacological inhibitors statistical analysis, we quantify epidermal factor (EGF)-induced signal processing individual over time dissect dynamic contribution downstream pathways. We define features encode information about ligand concentrations critical windows for inducing transitions. show both signal-regulated kinase (ERK) phosphatidylinositol 3-kinase (PI3K) activity necessary initial entry, whereas only PI3K affects duration S phase stages signaling.