Redefining Signaling Pathways with an Expanding Single-Cell Toolbox

Trends Biotechnol. 2016 Jun;34(6):458-469. doi: 10.1016/j.tibtech.2016.02.009. Epub 2016 Mar 9.


Genetically identical cells respond heterogeneously to uniform environmental stimuli. Consequently, investigating the signaling networks that control these cell responses using 'average' bulk cell measurements can obscure underlying mechanisms and misses information emerging from cell-to-cell variability. Here we review recent technological advances including live-cell fluorescence imaging-based approaches and microfluidic devices that enable measurements of signaling networks, dynamics, and responses in single cells. We discuss how these single-cell tools have uncovered novel mechanistic insights for canonical signaling pathways that control cell proliferation (ERK), DNA-damage responses (p53), and innate immune and stress responses (NF-κB). Future improvements in throughput and multiplexing, analytical pipelines, and in vivo applicability will all significantly expand the biological information gained from single-cell measurements of signaling pathways.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / physiology
  • Cell Separation / methods*
  • DNA Damage / physiology*
  • Gene Expression Profiling / methods
  • Humans
  • Immunity, Innate / immunology*
  • Lab-On-A-Chip Devices
  • MAP Kinase Signaling System / physiology*
  • Microscopy, Fluorescence / methods*
  • Oxidative Stress / physiology*
  • Tumor Suppressor Protein p53 / metabolism*


  • Tumor Suppressor Protein p53