Individual Cells Can Resolve Variations in Stimulus Intensity along the IGF-PI3K-AKT Signaling Axis

Sean M. Gross, Mark A. Dane, Elmar Bucher, Laura M. Heiser

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cells sense and respond to signals in their local environment by activating signaling cascades that lead to phenotypic changes. Differences in these signals can be discriminated at the population level; however, single cells have been thought to be limited in their capacity to distinguish ligand doses due to signaling noise. We describe here the rational development of a genetically encoded FoxO1 sensor, which serves as a down-stream readout of insulin growth factor-phosphatidylinositol 3-kinase IGF-PI3K-AKT signaling pathway activity. With this reporter, we tracked individual cell responses to multiple IGF-I doses, pathway inhibitors, and repeated treatments. We observed that individual cells can discriminate multiple IGF-I doses, and these responses are sustained over time, are reproducible at the single-cell level, and display cell-to-cell heterogeneity. These studies imply that cell-to-cell variation in signaling responses is biologically meaningful and support the endeavor to elucidate mechanisms of cell signaling at the level of the individual cell.

Original languageEnglish (US)
Pages (from-to)580-588.e4
JournalCell Systems
Volume9
Issue number6
DOIs
StatePublished - Dec 18 2019

Keywords

  • AKT
  • fluorescent reporters
  • FoxO1
  • IGF-I
  • information theory
  • live-cell imaging
  • signaling dynamics
  • signaling pathways
  • single cell

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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