Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation

J Cell Physiol. 2015 Jul;230(7):1403-12. doi: 10.1002/jcp.24888.

Abstract

The dynamics of heterogeneous clonal lineages within a cell population, in aggregate, shape both normal and pathological biological processes. Studies of clonality typically relate the fitness of clones to their relative abundance, thus requiring long-term experiments and limiting conclusions about the heterogeneity of clonal fitness in response to perturbation. We present, for the first time, a method that enables a dynamic, global picture of clonal fitness within a mammalian cell population. This novel assay allows facile comparison of the structure of clonal fitness in a cell population across many perturbations. By utilizing high-throughput imaging, our methodology provides ample statistical power to define clonal fitness dynamically and to visualize the structure of perturbation-induced clonal fitness within a cell population. We envision that this technique will be a powerful tool to investigate heterogeneity in biological processes involving cell proliferation, including development and drug response.

Publication types

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

MeSH terms

  • Cell Culture Techniques
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • Clone Cells
  • Cycloheximide / pharmacology
  • Gene Expression Regulation
  • Genetic Fitness
  • Humans
  • Protein Synthesis Inhibitors / pharmacology

Substances

  • Protein Synthesis Inhibitors
  • Cycloheximide